bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel de novo KDM5C variant in a female with global developmental delay and ataxia: a case report
Authors: Lippa Natalie C. , Barua Subit , Aggarwal Vimla , Pereira Elaine , Bain Jennifer M.
Published: September 2021

Background

Pathogenic variants in KDM5C are a cause of X-linked intellectual disability in males. Other features in males include short stature, dysmorphic features, seizures and spasticity. In some instances, female relatives were noted to have learning difficulties and mild intellectual disabilities, but full phenotypic descriptions were often incomplete. Recently, detailed phenotypic features of five affected females with de novo variants were described. (Clin Genet 98:43–55, 2020) Four individuals had a protein truncating variant and 1 individual had a missense variant. All five individuals had developmental delay/intellectual disability and three neurological features.

Case presentation

Here we report a three-year-old female with global developmental delay, hypotonia and ataxia. Through whole exome sequencing, a de novo c.1516A > G (p.Met506Val) variant in KDM5C was identified. This missense variant is in the jumonji-C domain of this multi domain protein where other missense variants have been previously reported in KDM5C related disorder. The KDM5C gene is highly intolerant to functional variation which suggests its pathogenicity. The probands motor delays and language impairment is consistent with other reported female patients with de novo variants in KDM5C. However, other features reported in females (distinctive facial features, skeletal abnormalities, short stature and endocrine features) were absent. To the best of our knowledge, our proband is the first female patient reported with a diagnosis of ataxia.

Conclusions

This case report provides evidence for an emerging and phenotypic variability that adds to the literature of the role of KDM5C in females with neurodevelopmental disorders as well as movement disorders.
Postpartum women’s psychological experiences during the COVID-19 pandemic: a modified recurrent cross-sectional thematic analysis
Authors: Jackson Leanne , De Pascalis Leonardo , Harrold Joanne A. , Fallon Victoria , Silverio Sergio A.
Published: September 2021

Background

COVID-19 has placed additional stressors on mothers during an already vulnerable lifecourse transition. Initial social distancing restrictions (Timepoint 1; T1) and initial changes to those social distancing restrictions (Timepoint 2; T2) have disrupted postpartum access to practical and emotional support. This qualitative study explores the postpartum psychological experiences of UK women during different phases of the COVID-19 pandemic and associated ‘lockdowns’.

Methods

Semi-structured interviews were conducted with 12 women, approximately 30 days after initial social distancing guidelines were imposed in the UK (22 April 2020). A separate 12 women were interviewed approximately 30 days after the initial easing of social distancing restrictions (10 June 2020). Data were transcribed verbatim, uploaded into NVivo for management and analysis, which followed a recurrent cross-sectional approach to thematic analysis.

Results

Two main themes were identified for T1: ‘Motherhood is Much Like Lockdown’ and ‘A Self-Contained Family Unit’. Each main T1 theme contained two sub-themes. Two main themes were also identified for T2: ‘Incongruously Held Views of COVID-19’ and ‘Mothering Amidst the Pandemic’. Each main T2 theme contained three sub-themes. Comparisons between data gathered at each timepoint identified increased emotional distress over time. Current findings call for the improvement of postpartum care by improving accessibility to social support, and prioritising the re-opening of schools, and face-to-face healthcare appointments and visitation.

Conclusion

Social distancing restrictions associated with COVID-19 have had a cumulative, negative effect on postpartum mental health. Recommendations such as: Allowing mothers to ‘bubble’ with a primary support provider even at their healthcare appointments; allowing one support partner to attend all necessary healthcare appointments; and providing tailored informational resources, may help to support postpartum emotional wellbeing during this, and similar health crises in the future.
Physician-patient communication of costs and financial burden of cancer and its treatment: a systematic review of clinical guidelines
Authors: Agarwal Anupriya , Livingstone Ann , Karikios Deme J. , Stockler Martin R. , Beale Philip J. , Morton Rachael L.
Published: September 2021

Background

Optimising the care of individuals with cancer without imposing significant financial burden related to their anticancer treatment is becoming increasingly difficult. The American Society of Clinical Oncology (ASCO) has recommended clinicians discuss costs of cancer care with patients to enhance shared decision-making. We sought information to guide oncologists’ discussions with patients about these costs.

Methods

We searched Medline, EMBASE and clinical practice guideline databases from January 2009 to 1 June 2019 for recommendations about discussing the costs of care and financial burden. Guideline quality was assessed with the AGREE-II instrument.

Results

Twenty-seven guidelines met our eligibility criteria, including 16 from ASCO (59%). 21 of 27 (78%) guidelines included recommendations about discussion or consideration of treatment costs when prescribing, with information about actual costs in four (15%). Recognition of the risk of financial burden or financial toxicity was described in 81% (22/27) of guidelines. However, only nine guidelines (33%) included information about managing the financial burden.

Conclusions

Current clinical practice guidelines have little information to guide physician-patient discussions about costs of anticancer treatment and management of financial burden. This limits patients’ ability to control costs of treatment, and for the healthcare team to reduce the incidence and severity of financial burden. Current guidelines recommend clinician awareness of price variability and high costs of treatment. Clinicians are recommended to explore cost concerns and address financial worries, especially in high risk groups. Future guidelines should include advice on facilitating cost transparency discussions, with provision of cost information and resources.
Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial
Authors: Ai Xinghao , Song Zhengbo , Jian Hong , Zhou Zhen , Chen Zhiwei , Yu Yongfeng , Li Ziming , Lu Shun
Published: September 2021

Background

Standard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. The clinical benefits with pan-HER inhibitors (afatinib, neratinib, and dacomitinib), anti-HER2 antibody drug conjugate (ADC) trastuzumab emtansine, and an emerging irreversible tyrosine kinase inhibitor (TKI) poziotinib were modest. Another new ADC trastuzumab deruxtecan showed encouraging outcomes, but only phase I study was completed. Pyrotinib, another emerging irreversible epidermal growth factor receptor (EGFR)/HER2 dual TKI, has been approved in HER2-positive breast cancer in 2018 in China. It has shown promising antitumor activity against HER2-mutant NSCLC in phase II trials, but pyrotinib-related diarrhea remains an issue. The antiangiogenic and immunomodulatory drug thalidomide is a cereblon-based molecular glue that can induce the degradation of the IKAROS family transcription factors IKZF1 and IKZF3. The use of thalidomide can also decrease gastrointestinal toxicity induced by anti-cancer therapy.

Methods

This is an open-label, single-arm phase II trial. A total of 39 advanced NSCLC patients with HER2 exon 20 insertions and ≤ 2 lines of prior chemotherapy will be recruited, including treatment-naïve patients who refuse chemotherapy. Patients are allowed to have prior therapy with immune checkpoint inhibitors and/or antiangiogenic agents. Those who have prior HER2-targeting therapy or other gene alterations with available targeted drugs are excluded. Eligible patients will receive oral pyrotinib 400 mg once daily and oral thalidomide 200 mg once daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate.

Discussion

The addition of thalidomide to pyrotinib is expected to increase the clinical benefit in advanced NSCLC patients with HER2 exon 20 insertions, and reduce the incidence of pyrotinib-related diarrhea. We believe thalidomide is the stone that can hit two birds.

Trial registration

ClinicalTrials.gov Identifier: NCT04382300. Registered on May 11, 2020.
Cervical cancer screening “see and treat approach”: real-life uptake after invitation and associated factors at health facilities in Gondar, Northwest Ethiopia
Authors: Destaw Alemnew , Midaksa Miresa , Addissie Adamu , Kantelhardt Eva Johanna , Gizaw Muluken
Published: September 2021

Background

Although cervical cancer is a preventable disease, screening coverage in Ethiopia is far below the target. There is limited evidence on uptake among the general population in Ethiopia. Thus, this study was conducted to assess uptake and associated factors with the cervical cancer screening “see and treat approach” among eligible women in public health facilities in Gondar town, Northwest Ethiopia.

Method

A facility-based, cross-sectional study was conducted. The total sample size was 493. A consecutive sampling method was applied. Participants were informed about and invited to cervical cancer screening using visual inspection with acetic acid. Crude and adjusted odds ratios were calculated to determine statistical association with socio-demographic variables. Multivariable logistic regression was used to determine factors of cervical cancer screening uptake.

Result

Out of 464 women advised for screening, 76 (16.4, 95% CI [13, 19.8%]) attended the screening. Primary education and above (AOR = 5.3, 95% CI [2.20, 13.0]), knowledge about the disease (AOR = 8.4, 95% CI [3.33, 21.21]), perceived susceptibility (AOR = 6.5, 95% CI [2.72, 15.51]), fewer perceived barriers (AOR = 6.4, 95% CI [2.30, 17.80]), cues to action (AOR = 4.6, 95% CI [1.86, 11.32]), perceived self-efficacy (AOR = 5, 95% CI [2.14, 11.73]), and previous recommendation for screening (AOR = 2.7, 95% CI [1.15, 6.51]) were significantly associated with screening uptake.

Conclusion

The actual uptake of screening offered in this study was high relative to only 3% national screening coverage. There is a need to implement active invitation for screening with special focus on less-educated women. Repeated invitation may facilitate future screening uptake.
Acute retinal necrosis caused by co-infection with multiple viruses in a natalizumab-treated patient: a case report and brief review of literature
Authors: Cheraqpour Kasra , Ahmadraji Aliasghar , Rashidinia Ali , Irannejad Maziyar , Shahriari Mansoor
Published: September 2021

Background

Acute retinal necrosis is considered a rare infectious uveitis. This condition is usually caused by varicella-zoster virus or herpes simplex virus. Acute retinal necrosis caused by co-infection with multiple viruses is extremely rare. Herein, we report a case of acute retinal necrosis caused by co-infection with herpes simplex virus (type I and II) and varicella-zoster virus (VZV) in a natalizumab-treated patient due to multiple sclerosis.

Case presentation

An adult man presented with a complaint of decreased vision of the right eye from 12 days ago. He was a known case of multiple sclerosis receiving natalizumab. Examination of the right eye revealed severe conjunctival injection, fine diffuse keratic precipitates, 3 + anterior chamber and vitreous cells, elevated intraocular pressure (26 mmHg), a blurred optic disk with hemorrhagic patches, and occlusive vasculitis plus confluent necrotizing patches in the peripheral retina compatible with diagnosis of acute retinal necrosis. He underwent anterior chamber and vitreous tap, and real-time PCR detected HSV I & II and VZV on the vitreous specimen. A second PCR showed the same result. After neurological consultation, natalizumab was discontinued and intravenous acyclovir was started followed by oral acyclovir and oral prednisolone to control the disease, which was successful.

Conclusions

Although rare, multiple-viral infection should be considered in the physiopathology of acute retinal necrosis, especially in immunosuppressed patients.
Developing trauma resilient communities through community capacity-building
Authors: Gilmer Todd P. , Center Kimberly , Casteel Danielle , Choi Kyle , Innes-Gomberg Debbie , Lansing Amy E.
Published: September 2021

Background

Trauma is a significant public health issue, negatively impacting a range of health outcomes. Providers and administrators in public mental health systems recognize the widespread experience of trauma, as well as their limited ability to address trauma within their communities. In response, the Los Angeles County Department of Mental Health funded nine regionally based community partnerships to build capacity to address trauma. We describe partnership and community capacity-building efforts and examine community impact, defined as successful linkages to resources and changes in stress tolerance capacities among community members.

Methods

We conceptualized community capacity-building as dissemination of trauma-informed education and training, community outreach and engagement, and linkage of community members to resources. We measured trauma-informed trainings among partnership members (N = 332) using the Trauma-Informed Organizational Toolkit. Outreach, engagement and linkages were documented using Event and Linkage Trackers. We examined changes in the type of successful linkage after the issuance of statewide mandatory restrictions in response to COVID-19. We examined changes in stress tolerance capacities among community members (N = 699) who were engaged in ongoing partnership activities using the 10-item Conner-Davidson Resilience Scale; the 28-item Coping Orientation to Problems; and the pictorial Inclusion of Community in Self Scale.

Results

Training and education opportunities were widespread: 66% of members reported opportunities for training in 13 or more trauma-informed practices. Partnerships conducted over 7800 community capacity-building events with over 250,000 attendees. Nearly 14,000 successful linkages were made for a wide range of resources, with consistent linkage success prior to (85%) and during (87%) the pandemic. In response to COVID-19, linkage type significantly shifted from basic services and health care to food distribution (p < .01). Small but significant improvements occurred in coping through emotional and instrumental support; and sense of community connectedness (p < .05 each).

Conclusions

Community-based partnerships demonstrated effective capacity-building strategies. Despite the pandemic, community members did not report reduced stress tolerance, instead demonstrating gains in external help-seeking (use of emotional and instrumental supports) and perception of community connectedness. Future work will use qualitative methods to examine the impact of community capacity-building and the sustainability of this approach for addressing the impact of trauma within communities.
Associations between neighbourhood deprivation and engagement in arts, culture and heritage: evidence from two nationally-representative samples
Authors: Mak Hei Wan , Coulter Rory , Fancourt Daisy
Published: September 2021

Background

Previous research has shown the benefits of arts and cultural engagement for physical, mental and social wellbeing. This engagement is socially and geographically patterned. Yet it remains unclear whether place-based attributes are associated with engagement behaviour independent of individual factors. Therefore, the aim of this cross-sectional study was to robustly disentangle associations between geographical deprivation and arts engagement from the individual socio-demographic factors that tend to correlate with residential locations.

Methods

Two different samples drawn from two representative surveys of adults living in England were compared – Understanding Society Wave 2 (2010/12) (N = 14,782) and Taking Part survey (2010/11) (N = 4575). Propensity score matching (PSM) was applied to investigate the association between neighbourhood deprivation (20% most deprived vs 20% least deprived) and arts engagement (arts participation, cultural attendance and museums and heritage engagement).

Results

Higher levels of neighbourhood deprivation were associated with lower arts, culture and heritage engagement independent of individuals’ demographic backgrounds, socio-economic characteristics and regional locations. When exploring subcategories of deprivation, similar results were obtained across deprivation domains. Results were also consistent when using more distinct categories of deprivation (i.e. 10% most deprived vs 10% least deprived) and when comparing people living in the 20% most deprived neighbourhoods with those living in the 40% medium-deprived areas.

Conclusion

This study is the first to apply a robust PSM technique to examine the association between neighbourhood deprivation and arts engagement using two nationally-representative samples. Results show that neighbourhood deprivation may act as a barrier that could prevent people from engaging in the arts, which in turn may exacerbate social and health inequalities. This highlights the importance of place-based schemes that focus on increasing individual motivation and capacity to engage in arts and cultural activities, especially in areas of high deprivation.
How can social insurers promote return to work in occupational rehabilitation? A quantitative, cross-sectional study
Authors: Pasanen Jarna , Luoma Arto
Published: September 2021

Background

Earlier studies indicate a correlation between disability claims experience and return to work outcomes. Thus, the insurer’s role and actions may affect the self-rated health of the disabled worker and the outcomes of occupational rehabilitation. This study diversifies the existing empirical evidence on the role of the insurer in the rehabilitation process and reveals the critical actions that best promote success.

Materials and methods

Explorative factor analysis (EFA) and confirmatory factor analysis (CFA), followed by binary regression, were used to analyse survey data of disabled workers (n = 661) who had undergone an occupational rehabilitation within an earnings-related pension insurance system in Finland.

Results

The claimant’s perceptions of the insurer’s (1) high-quality informing and guidance, (2) customer orientation, (3) smooth process flow and (4) positive service attitude had substantial and statistically significant effects on the success of occupational rehabilitation after adjusting for all likely confounding variables.

Conclusions

The insurer’s actions are significant predictors of the outcome of occupational rehabilitation. The insurer can promote the health of rehabilitees most effectively by ensuring a smooth process flow and adopting a customer-oriented approach.
18F-FDG PET/CT predicts acute exacerbation in idiopathic pulmonary fibrosis after thoracic surgery
Authors: Yoon Hee-Young , Lee Suk Hyun , Ha Sejin , Ryu Jin-Sook , Song Jin Woo
Published: September 2021

Background

Acute exacerbation (AE) is the most lethal postoperative complication in idiopathic pulmonary fibrosis (IPF); however, prediction before surgery is difficult. We investigated the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting postoperative AE in IPF.

Method

Clinical data of 48 IPF patients who underwent 18F-FDG PET/CT before thoracic surgery were retrospectively analyzed. Mean and maximal standardized uptake values (SUVmean and SUVmax, respectively) were measured in the fibrotic area. Additionally, adjusted values-SUV ratio (SUVR, defined as SUVmax-to-liver SUVmean ratio), tissue fraction-corrected SUVmean (SUVmeanTF), and SUVR (SUVRTF)-were calculated.

Results

The mean age of the subjects was 67.8 years and 91.7% were male. After thoracic surgery, 21 (43.8%) patients experienced postoperative complications including prolonged air leakage (29.2%), death (14.6%), and AE (12.5%) within 30 days. Patients who experienced AE showed higher SUVmax, SUVR, SUVmeanTF, and SUVRTF than those who did not, but other clinical parameters were not different between patients with and without AE. The SUV parameters did not differ for other complications. The SUVR (odds ratio [OR] 29.262; P = 0.030), SUVmeanTF (OR 3.709; P = 0.041) and SUVRTF (OR 20.592; P = 0.017) were significant predicting factors for postoperative AE following a multivariate logistic regression analysis. On receiver operating characteristics curve analysis, SUVRTF had the largest area under the curve (0.806, P = 0.007) for predicting postoperative AE among SUV parameters.

Conclusions

Our findings suggest that 18F-FDG PET/CT may be useful in predicting postoperative AE in IPF patients and among SUVs, SUVRTF is the best parameter for predicting postoperative AE in IPF patients.
Prevalence of dental caries in Pakistan: a systematic review and meta-analysis
Authors: Siddiqui Ammar Ahmed , Alshammary Freah , Mulla Mushir , Al-Zubaidi Saad M. , Afroze Eman , Amin Junaid , Amin Salman , Shaikh Sameer , Madfa Ahmed A. , Alam Mohammad Khursheed
Published: September 2021

Background

Optimum oral health is impossible to achieve without managing dental caries. The first step to manage dental caries at a community level is to know its prevalence and trend. Unfortunately, the prevalence of dental caries at the national/regional level is not known in many developing countries. Pakistan is no exception. The present meta-analysis was planned to document the prevalence of dental caries at the national, as well as regional level. This paper will serve as a baseline for making future health policies, and health promotion activities in the country.

Methods

Literature was searched through various databases, such as PubMed, SCOPUS, and Web of science using: "Prevalence", "Dental Caries", "Dental Decay" and "Severity" as keywords. Any study that reported the prevalence of dental caries, and was conducted in the Pakistani population was included. Thirty studies fulfilled the inclusion criteria. Quality assessment of all the included studies was performed using Joanna Briggs Institute (JBI) critical appraisal checklist for prevalence studies. MedCalc software was used to analyze the data.

Results

In total 27,878 subjects were included in a meta-analysis from 30 studies. The prevalence estimate of dental caries at the national level was 56.62% (95% CI: 49.54 to 63.57). The I2 value was 99.07% (95% CI: 98.94 to 99.18), (I2 > 75%) indicating heterogeneity, hence pooled proportion was reported using a random-effect model. The prevalence estimate of dental caries in Sindh was 58.946% (95% CI: 43.796 to 73.274), and in Punjab, it was 55.445% (95% CI: 44.174 to 66.44), whilst in Baluchistan and KPK combined was 51.168% (95% CI: 22.930 to 79.004).

Conclusion

Based on the existing data nearly 60% of the Pakistani population have dental caries. The proportion is almost the same in all provinces. Most of the included studies were found to be of high risk.
Allergy-related diseases in childhood and risk for abdominal pain-related functional gastrointestinal disorders at 16 years—a birth cohort study
Authors: Sjölund Jessica , Kull Inger , Bergström Anna , Järås Jacob , Ludvigsson Jonas F. , Törnblom Hans , Simrén Magnus , Olén Ola
Published: September 2021

Background

Studies on allergy-related diseases in relation to abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) in children are few and results are contradictory. We examined the associations between childhood allergy-related diseases and adolescent AP-FGIDs in general and irritable bowel syndrome (IBS) in particular.

Method

Prospective population-based birth cohort study of 4089 children born in Sweden 1994-1996. We analysed data from 2949 children with complete follow-up at 16 years (y) and no diagnosis of inflammatory bowel disease or coeliac disease at 12y or 16y. Asthma, rhinitis, eczema, and food hypersensitivity (FH) were assessed through questionnaires at 1–2y, 4y, 8y, 12y, and 16y. AP-FGIDs and IBS were assessed through questionnaires at 16y and defined according to the Rome III criteria. Associations between childhood allergy-related diseases and any AP-FGID and IBS and 16y respectively were examined using binomial generalized linear models with a log link function and described as relative risk with 95% confidence intervals.

Results

The prevalence of any AP-FGID and IBS at 16y were 12.0% and 6.0% respectively. Eczema at 1–2y, 4y, and 8y, and FH at 12y and 16y were associated with an increased risk for any AP-FGID at 16y. Asthma and FH at 12y and 16y were associated with an increased risk for IBS at 16y. The relative risk for IBS at 16y increased with increasing number of concurrent allergy-related diseases at 16y, but linear trend for relative risk was only borderline statistically significant (P for trend = 0.05).

Conclusions

This prospective population-based study demonstrated positive associations between childhood allergy-related diseases and adolescent AP-FGIDs, including IBS, implicating shared pathophysiology among these disorders.
High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer
Authors: Zhao Zongxian , Li Shuliang , Li Shilong , Wang Jun , Lin Hai , Fu Weihua
Published: September 2021

Background

Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer.

Methods

The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation.

Results

CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001).

Conclusion

CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC.
MiR-613 inhibits the proliferation, migration, and invasion of papillary thyroid carcinoma cells by directly targeting TAGLN2
Authors: Huang Yonglian , Zhang Hengwei , Wang Lidong , Liu Chenxi , Guo Mingyue , Tan Hao , Liu Zhen
Published: September 2021

Background

Papillary thyroid carcinoma (PTC), with a rapidly increasing incidence, is the most prevalent malignant cancer of the thyroid. However, its pathogenesis is unclear and its specific clinical indicators have not yet been identified. There is increasing evidence that microRNAs (miRNAs) play important roles in tumor occurrence and progression. Specifically, miR-613 participates in the regulation of tumor development in various cancers; however, its effects and mechanisms of action in PTC are still unclear. Therefore, in this study, we investigated the expression and function of miR-613 in PTC.

Methods

qRT-PCR was used to determine miR-613 expression in 107 pairs of PTC and adjacent-normal tissues as well as in PTC cell lines and to detect TAGLN2 mRNA expression in PTC tissues and adjacent normal tissues. Western blot analysis was performed to identify TAGLN2 and epithelial–mesenchymal transition (EMT) biomarkers. The effects of miR-613 on PTC progression were evaluated by performing MTS, wound-healing, and Transwell assays in vitro. Luciferase reporter assays were also performed to validate the target of miR-613.

Results

In PTC, miR-613 was significantly downregulated and its low expression level was associated with cervical lymph node metastasis. However, its overexpression significantly suppressed PTC cell proliferation, migration, and invasion and inhibited EMT. TAGLN2 was identified as a target of miR-613, which also significantly inhibited the expression of TAGLN2. Further, the restoration of TAGLN2 expression attenuated the inhibitory effects of miR-613 on PTC cell proliferation and metastasis.

Conclusion

Our findings demonstrated that miR-613 can suppress the progression of PTC cells by targeting TAGLN2, indicating that miR-613 plays the role of a tumor suppressor in PTC. Overall, these results suggest that the upregulation of miR-613 is a promising therapeutic strategy for PTC.
MicroRNA-550a-3-5p controls the brain metastasis of lung cancer by directly targeting YAP1
Authors: Wei Liang , Wang Guangxue , Yang Cheng , Zhang Yanfei , Chen Yiming , Zhong Chunlong , Li Qinchuan
Published: September 2021

Background

This study aimed to explore the potential regulatory mechanisms of brain metastasis and to identify novel underlying targets of lung cancer with brain metastasis.

Methods

Exosomes were isolated from the plasma of lung cancer patients with or without brain metastasis and low or high metastatic lung cancer cells, and small RNA from plasma-derived exosomes were sequenced. Differentially expressed miRNAs (DE-miRNAs) were identified. Human brain microvascular endothelial cells (HBMECs) were transfected with miR-550a-3-5p mimics or inhibitors and exosomes. Cell viability, migration, and apoptosis/cycle were determined using Cell Counting Kit-8 (CCK-8), Transwell, and flow cytometry, respectively. Western blotting was used to measure the expression of the associated proteins. Finally, a dual-luciferase reporter gene assay was performed to confirm the miR-550a-3-5p target.

Results

Transmission electron microscopy, NanoSight, and western blotting showed that exosomes were successfully isolated and cell-derived exosomes could be taken up by HBMECs. Sequencing identified 22 DE-miRNAs which were enriched in the MAPK, chemokine, PPAR, and Wnt signaling pathways. MiR-550a-3-5p was significantly enriched in brain metastatic exosomes. Cellular experiments showed that miR-550a-3-5p and exosome enrichment significantly inhibited cell viability and migration, promoted apoptosis, and regulated the cell cycle of HBMECs compared with the controls (P  <  0.05). Compared with the controls, high levels of both miR-550a-3-5p and exosomes markedly upregulated cleaved-PARP expression, but downregulated the expression of pRB, CDK6, YAP1, CTGF, and CYR61 (P  <  0.05). Finally, YAP1 was confirmed to bind directly to miR-550a-3-5p.

Conclusion

Our results indicate that miR-550a-3-5p and YAP1 may be novel potential targets for controlling brain metastasis.
Nanoceria seed priming enhanced salt tolerance in rapeseed through modulating ROS homeostasis and α-amylase activities
Authors: Khan Mohammad Nauman , Li Yanhui , Khan Zaid , Chen Linlin , Liu Jiahao , Hu Jin , Wu Honghong , Li Zhaohu
Published: September 2021

Background

Salinity is a big threat to agriculture by limiting crop production. Nanopriming (seed priming with nanomaterials) is an emerged approach to improve plant stress tolerance; however, our knowledge about the underlying mechanisms is limited.

Results

Herein, we used cerium oxide nanoparticles (nanoceria) to prime rapeseeds and investigated the possible mechanisms behind nanoceria improved rapeseed salt tolerance. We synthesized and characterized polyacrylic acid coated nanoceria (PNC, 8.5 ± 0.2 nm, −43.3 ± 6.3 mV) and monitored its distribution in different tissues of the seed during the imbibition period (1, 3, 8 h priming). Our results showed that compared with the no nanoparticle control, PNC nanopriming improved germination rate (12%) and biomass (41%) in rapeseeds (Brassica napus) under salt stress (200 mM NaCl). During the priming hours, PNC were located mostly in the seed coat, nevertheless the intensity of PNC in cotyledon and radicle was increased alongside with the increase of priming hours. During the priming hours, the amount of the absorbed water (52%, 14%, 12% increase at 1, 3, 8 h priming, respectively) and the activities of α-amylase were significantly higher (175%, 309%, 295% increase at 1, 3, 8 h priming, respectively) in PNC treatment than the control. PNC primed rapeseeds showed significantly lower content of MDA, H2O2, and •O2− in both shoot and root than the control under salt stress. Also, under salt stress, PNC nanopriming enabled significantly higher K+ retention (29%) and significantly lower Na+ accumulation (18.5%) and Na+/K+ ratio (37%) than the control.

Conclusions

Our results suggested that besides the more absorbed water and higher α-amylase activities, PNC nanopriming improves salt tolerance in rapeseeds through alleviating oxidative damage and maintaining Na+/K+ ratio. It adds more knowledge regarding the mechanisms underlying nanopriming improved plant salt tolerance.

Graphical abstract
“It is the One Thing that has Worked”: facilitators and barriers to switching to nicotine salt pod system e-cigarettes among African American and Latinx people who smoke: a content analysis
Authors: Pulvers Kim , Rice Myra , Ahluwalia Jasjit S. , Arnold Michael J. , Marez Crystal , Nollen Nicole L.
Published: September 2021

Background

Electronic cigarettes are a harm reduction strategy for individuals who smoke cigarettes who cannot or do not want to quit using FDA-approved cessation methods. Identifying perceived facilitators and barriers to switching among people who smoke cigarettes is critical to optimizing health impact. This is particularly important for the most dominant e-cigarette device, nicotine salt pod electronic cigarettes. We investigate the experience using pod electronic cigarettes among African American and Latinx individuals who smoke, the two largest racial/ethnic minority groups who experience significant health disparities.

Methods

From July 2018 to May 2019, adults who smoked cigarettes, age 21 + (N = 114; M age = 44.6, 59.6% male, 52.6% African American from Kansas City, 47.4% Latinx from San Diego) received JUUL-brand electronic cigarettes (referred to hereafter as JUUL) for 6 weeks and answered interview questions at week six. We inquired what they liked and disliked about using JUUL, what helped with switching and made switching difficult, future intentions for continued JUUL use, and how JUUL compared to past smoking reduction methods. Responses were coded into themes by independent raters. Theme frequencies were analyzed separately by race/ethnicity and week 6 use trajectory (exclusive JUUL use, dual JUUL and cigarette use, exclusive cigarette use).

Results

Clean/smell was the aspect of using JUUL most commonly liked (23%), followed by convenience (19%). Coughing/harshness was a more common barrier to switching for African American (44%) than Latinx (9%), and for continuing cigarette use (56%) than for those who exclusively switched or dually used JUUL and combustible cigarettes (15–21%). Most (78% African American; 90% Latinx) reported that the benefits of using JUUL outweighed barriers, and this varied by JUUL use trajectory: 94% exclusive switch, 86% dual use, and 42% continued cigarette use. The majority said they would continue using JUUL to replace cigarettes (83% African American; 94% Latinx) and that JUUL worked better than other methods to reduce cigarettes (72%).

Conclusion

African American and Latinx individuals who smoked experience using pod electronic cigarettes was generally positive. Understanding facilitators and impediments to switching to electronic cigarettes among racial/ethnic minority people who smoke can inform harm reduction interventions and reduce tobacco-related health disparities.

Trial Registration ClinicalTrials.gov Identifier: NCT03511001 posted April 27, 2018.
Effects of differential measurement error in self-reported diet in longitudinal lifestyle intervention studies
Authors: Aaby David , Siddique Juned
Published: September 2021

Background

Lifestyle intervention studies often use self-reported measures of diet as an outcome variable to measure changes in dietary intake. The presence of measurement error in self-reported diet due to participant failure to accurately report their diet is well known. Less familiar to researchers is differential measurement error, where the nature of measurement error differs by treatment group and/or time. Differential measurement error is often present in intervention studies and can result in biased estimates of the treatment effect and reduced power to detect treatment effects. Investigators need to be aware of the impact of differential measurement error when designing intervention studies that use self-reported measures.

Methods

We use simulation to assess the consequences of differential measurement error on the ability to estimate treatment effects in a two-arm randomized trial with two time points. We simulate data under a variety of scenarios, focusing on how different factors affect power to detect a treatment effect, bias of the treatment effect, and coverage of the 95% confidence interval of the treatment effect. Simulations use realistic scenarios based on data from the Trials of Hypertension Prevention Study. Simulated sample sizes ranged from 110-380 per group.

Results

Realistic differential measurement error seen in lifestyle intervention studies can require an increased sample size to achieve 80% power to detect a treatment effect and may result in a biased estimate of the treatment effect.

Conclusions

Investigators designing intervention studies that use self-reported measures should take differential measurement error into account by increasing their sample size, incorporating an internal validation study, and/or identifying statistical methods to correct for differential measurement error.
Physical activity in out of school hours care: an observational study
Authors: Crowe Ruth K. , Probst Yasmine C. , Stanley Rebecca M. , Ryan Sarah T. , Weaver R. Glenn , Beets Michael W. , Norman Jennifer A. , Furber Susan E. , Vuong Cecilia , Hammersley Megan L. , Wardle Karen , Franco Lisa , Davies Marc , Innes-Hughes Christine , Okely Anthony D.
Published: September 2021

Background

Opportunities for physical activity within out of school
hours care (OSHC) are not well documented in Australia. This study explored factors associated with children (5–12 years) meeting 30 min of moderate to vigorous physical activity (MVPA) while attending OSHC in the afternoon period.

Methods

A cross-sectional study, conducted in 89 OSHC services in New South Wales, Australia, serving 4,408 children. Each service was visited twice between 2018–2019. Physical activity promotion practices were captured via short interviews and System for Observing Staff Promotion of Physical Activity and Nutrition (SOSPAN). Physical activity spaces was measured (m2) and physical activity of 3,614 child days (42% girls), were collected using Acti-Graph accelerometers. Association between program practices and children accumulation of MVPA was tested using mixed effects logistic regression, adjusted by OSHC service and child.

Results

Twenty-six percent of children (n = 925) accumulated 30 min or more of MVPA. Factors associated with children reaching MVPA recommendations included: services scheduling greater amounts of child-led free play, both 30–59 min (OR 2.6, 95%CI 1.70, 3.98) and ≥ 60 min (OR 6.4, 95%CI 3.90, 10.49); opportunities for staff-led organised play of ≥ 30 min (OR 2.3, 95%CI 1.47, 3.83); and active games that engaged the majority of children (OR 1.7, 95%CI 1.11, 2.61). Children were less likely to meet MVPA recommendations if services played games with elimination components (OR 0.56, 95%CI 0.37, 0.86).

Conclusion

Improvements to service-level physical activity promotion practices, specifically the type of physical activity scheduled and the structure of games, may be an effective strategy to increase MVPA of children attending OSHC afterschool in NSW, Australia.
IL-18 binding protein suppresses IL-17-induced osteoclastogenesis and rectifies type 17 helper T cell / regulatory T cell imbalance in rheumatoid arthritis
Authors: Min Hong Ki , Kim Sehee , Lee Ji-Yeon , Kim Kyoung-Woon , Lee Sang-Heon , Kim Hae-Rim
Published: September 2021

Background

Patients with rheumatoid arthritis (RA) have increased levels of interleukin-18 (IL-18) and decreased levels of IL-18 binding protein (IL-18BP) in the serum and synovial fluid (SF) compared to those in patients with osteoarthritis (OA) or in healthy controls. In this study, we evaluated the effects of IL-18BP on osteoclastogenesis and T cell differentiation in RA in vitro.

Methods

Serum and SF of patients with RA and OA were collected to compare IL-18 and IL-18BP levels by the enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) and SF mononuclear cells (SFMCs) of RA patients were cultured under type 17 helper T cell (Th17) polarisation conditions with or without IL-18BP. In addition, PBMCs were cultured in the presence of receptor activator of nuclear factor kappa-Β ligand (RANKL) or IL-17A with or without IL-18BP, and tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative polymerase chain reaction for expression levels of osteoclast-related genes were performed.

Results

IL-18 levels were higher in the serum and SF of patients with RA, whereas IL-18BP was lower in the SF of patients with RA than in the control group. Treatment of patients’ PBMCs with IL-18BP decreased the differentiation of CD4+ IL-17A+ and CD4+ RANKL+ T cells, whereas the differentiation of CD4+CD25highFOXP3+ T cell population increased in a dose-dependent manner. These changes in CD4+ T cell differentiation were also observed in the SFMCs of patients with RA. The levels IL-17A and soluble RANKL in the culture medium were significantly decreased by IL-18BP. IL-18BP administration decreased TRAP+ cell counts in a dose-dependent manner on the background of stimulation with RANKL-and IL-17A. In addition, expression levels of TRAP, NFATC1, CTSK, and TNFRSF11A (RANK) genes were lower in the IL-18BP treated cells.

Conclusion

We showed that IL-18BP can rectify the Th17/Treg imbalance and decrease IL-17-induced osteoclastogenesis in PBMCs from patients with RA. Therefore, IL-18BP may have therapeutic potential for RA treatment.
Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis: a prospective cohort study
Authors: Kindgren Erik , Ludvigsson Johnny
Published: September 2021

Background

The aetiology of juvenile idiopathic arthritis (JIA) is poorly understood. It has been shown that use of antibiotics is associated with JIA. However, whether the association is due to increased occurrence of infection in these individuals is unknown. The purpose of this investigation was to measure the association between number of infections and use of antibiotics during childhood with development of JIA.

Methods

In ABIS (All Babies in Southeast Sweden) a population-based prospective birth cohort of 17,055 children, data were collected on infections and antibiotic exposure during pregnancy and childhood. 102 individuals with JIA were identified. Multivariable logistic regression analyses were performed, adjusting for confounding factors.

Results

Exposure to antibiotics during the periods 1–12 months, 1–3 years and 5–8 years was significantly associated with increased risk for JIA. The odds of developing JIA were three times higher in those exposed to antibiotics during the first 3 years of life compared with those not exposed (aOR 3.17; 95% CI 1.11–9.03, p = 0.031), and more than twice as high in those exposed to antibiotics during the first 5 years of life compared with those not exposed (aOR 2.18; 95% CI 1.36–3.50, p = 0.001). The odds of developing JIA were 78% higher in those exposed to antibiotics during the first 8 years of life compared with those not exposed (aOR 1.78; 95% CI 1.15–2.73, p = 0.009). Occurrence of infection during fetal life or childhood showed no significant association with the risk of developing JIA, after confounder adjustment.

The cumulative number of courses of antibiotics was significantly higher during childhood for the individuals who developed JIA (p < 0.001). Penicillins were more frequently used than non-penicillins, but both had an equal effect on the risk of developing JIA.

Conclusions

Exposure to antibiotics early in life is associated with later onset of JIA in a large birth cohort from the general population. The relationship was dose dependent. These results suggest that further, more restrictive, antibiotic policies during the first years of life would be advisable.