bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.