bluuebunny/crossref_metadata_2025 huggingface dataset:
RAGE signaling during tobacco smoke-induced lung inflammation and potential therapeutic utility of SAGEs
Authors: Hirschi-Budge Kelsey M. , Tsai Kary Y. F. , Curtis Katrina L. , Davis Gregg S. , Theurer Benjamin K. , Kruyer Anica M. M. , Homer Kyle W. , Chang Ashley , Van Ry Pam M. , Arroyo Juan A. , Reynolds Paul R.
Published: April 2022

Background

Smoke exposure culminates as a progressive lung complication involving airway inflammation and remodeling. While primary smoke poses the greatest risk, nearly half of the US population is also at risk due to exposure to secondhand smoke (SHS).

Methods

We used WT, RAGE−/− (KO), and Tet-inducible lung-specific RAGE overexpressing transgenic (TG) mice to study the role of RAGE during short-term responses to SHS. We evaluated SHS effects in mice with and without semi-synthetic glycosaminoglycan ethers (SAGEs), which are anionic, partially lipophilic sulfated polysaccharide derivatives known to inhibit RAGE signaling. TG Mice were weaned and fed doxycycline to induce RAGE at postnatal day (PN) 30. At PN40, mice from each line were exposed to room air (RA) or SHS from three Kentucky 3R4F research cigarettes via a nose-only delivery system (Scireq Scientific, Montreal, Canada) five days a week and i.p. injections of PBS or SAGE (30 mg/kg body weight) occurred three times per week from PN40-70 before mice were sacrificed on PN70.

Results

RAGE mRNA and protein expression was elevated following SHS exposure of control and TG mice and not detected in RAGE KO mice. Bronchoalveolar lavage fluid (BALF) analysis revealed RAGE-mediated influence on inflammatory cell diapedesis, total protein, and pro-inflammatory mediators following exposure. Lung histological assessment revealed indistinguishable morphology following exposure, yet parenchymal apoptosis was increased. Inflammatory signaling intermediates such as Ras and NF-κB, as well as downstream responses were influenced by the availability of RAGE, as evidenced by RAGE KO and SAGE treatment.

Conclusions

These data provide fascinating insight suggesting therapeutic potential for the use of RAGE inhibitors in lungs exposed to SHS smoke.
Comparison of postoperative cough-related quality of life and recovery between sublobectomy and lobectomy for early-stage non-small cell lung cancer patients: a longitudinal study
Authors: Lin Rongjia , Chen Wen , Zhu Leilei , Pan Xiaojie
Published: April 2022

Background

Cough is a common complication after pulmonary surgery. Previous studies lacked a standard measure to assess postoperative cough-related quality of life and recovery. The purpose of this study is to compare postoperative cough regarding changes in health-related quality of life (HRQOL) and recovery trajectory between video-assisted thoracic surgery (VATS) lobectomy and sublobectomy (segmentectomy or wedge resection) for early-stage non-small cell lung cancer (NSCLC) patients via the Leicester Cough Questionnaire in Mandarin Chinese (LCQ-MC).

Methods

Overall, 156 patients with NSCLC underwent either VATS lobectomy or VATS sublobectomy; LCQ-MC was used to report the impact of postoperative cough on HRQOL for 6 months after surgery. The total scores of LCQ-MC range from 3 to 21, with a higher score indicating better health. Recovery from postoperative cough was defined as LCQ-MC scores returning to preoperative levels. The sensitivity of LCQ-MC to changes in postoperative cough recovery over time was evaluated via its ability to distinguish between surgery types.

Results

The VATS sublobectomy group reported significantly higher mean LCQ-MC scores at 1 month after surgery, but no significant difference postoperatively at 3 and 6 months after surgery, and returned to preoperative physical (69 vs. 99 days), psychological (67 vs. 99 days), social (50 vs. 98 days) and total (69 vs. 99 days) scores faster than the VATS lobectomy group (all p < 0.05).

Conclusion

VATS sublobectomy had generally better HRQOL and faster recovery of postoperative cough than VATS lobectomy. In addition, the LCQ-MC performed satisfactorily in describing the longitudinal changes in postoperative cough.
Dental characteristics associated with methamphetamine use: analysis using forensic autopsy data
Authors: Mizuno Satomi , Ono Sachiko , Takano Ayumi , Yasunaga Hideo , Iwase Hirotaro
Published: April 2022

Background

Little is known regarding the oral conditions in nonelderly methamphetamine users, such as the presence of dental caries and periodontitis. We aimed the oral conditions between methamphetamine users and non-users stratified by age groups.

Methods

In this cross-sectional study, computed tomography images were obtained from 3,338 decedents at two forensic medicine departments in Japan. Decedents aged > 20 or ≤ 64 years were included in the study and categorised into methamphetamine-detected (MA) and undetected (control) groups based on toxicological examinations. Decedents in the MA and control groups were matched for age and sex in a 1:4 ratio. The matched pairs were further categorised into young adults (20–44 years) and middle-aged adults (45–64 years). Oral characteristics, including the decayed, missing, and filled teeth (DMFT) index; periodontitis; distributional patterns of each tooth condition; and occlusal status, were compared between the MA and control groups for each age category. Among 3,338 decedents, 37 young and 55 middle-aged adults in the MA group were matched with 148 and 220 adults in the control group, respectively.

Results

In the young adult group, methamphetamine use was significantly associated with higher DMFT index (mean [standard deviation], 14.2 [7.6] vs 11.0 [6.1];p = 0.007), smaller number of filled teeth (2.8 [2.9] vs 5.3 [4.0];p = 0.001), higher proportion of periodontitis (39.0% vs 6.8%;p < 0.001), and lower proportion of occlusal support (54.1% vs 81.1%;p = 0.001). Young adult methamphetamine users tended to have untreated decayed canines and molars and missing molars. These findings were similar to those in middle-aged adults except the tendency to have missing maxillary incisors.

Conclusions

Nonelderly methamphetamine users had distinctive oral characteristics that may help screen for methamphetamine abuse through dental examinations.
The training effects of a continuing education program on nurses’ knowledge and attitudes to palliative care: a cross sectional study
Authors: Chen Xian , Zhang Yuxi , Arber Anne , Huo Xiaorong , Liu Jin , Sun Cuihua , Yuan Ling , Wang Xuemei , Wang Dan , Wu Jinfeng , Du Junjie
Published: April 2022

Background

Most nurses in China have not been trained to take care of end-of-life patients appropriately due to lack of educational resources and insufficient training. A palliative care program was launched by the Jiangsu Nursing Association (JNA training program) and to identify gaps in palliative care training. The main aim of this study was to evaluate the training effects of the JNA training program on nurses’ knowledge and attitudes to palliative care.

Methods

A cross-sectional study was conducted with 10 048 registered nurses in all regions of Jiangsu. All participants completed an online questionnaire using the Chinese version of The Palliative Care Quiz for Nursing (PCQN-C) and the Frommelt Attitude Toward Care of the Dying scale (FATCOD-B-C). A propensity score matched analysis was performed between the nurses who had attended the JNA training program and whose who hadn’t.

Results

The average score of PCQN-C among all nurses was 8.79, while the mean score of the FATCOD-B-C was 103.62. Those participants who attended the JNA training program had significantly better scores than those who did not. Propensity score matching analysis showed that the palliative care training program failed to improve nurses’ knowledge in psychosocial and spiritual care or their attitudes towards the necessity of family support although there was positive impact on other aspects of palliative care.

Conclusions

Knowledge of palliative care among Chinese nurses remains low. Training programs may improve general knowledge and attitudes to palliative care. However, important aspects of knowledge such as communication skills, family support, and psychosocial aspects of care, are missing. These gaps should be filled in future palliative care training programs targeting nurses with oriental culture background.
Effectiveness of home-based pulmonary rehabilitation programs for patients with chronic obstructive pulmonary disease (COPD): systematic review
Authors: Stafinski Tania , Nagase Fernanda Inagaki , Avdagovska Melita , Stickland Michael K. , Menon Devidas
Published: April 2022

Background

Although pulmonary rehabilitation (PR) is considered a key component in managing chronic obstructive pulmonary disease (COPD) patients, uptake remains suboptimal. This systematic review aimed to determine the effectiveness of home-based PR (HBPR) programs for COPD patients.

Methods

A systematic review of scholarly literature published within the last 10 years from the conception of this project was conducted using internationally recognized guidelines. Search strategies were applied to electronic databases and clinical trial registries through March 2020 and updated in November 2021 to identify studies comparing HBPR with ‘usual care’ or outpatient pulmonary rehabilitation (OPR). To critically appraise randomized studies, the Cochrane Collaboration risk of bias tool (ROB) was used. The quality of non-randomized studies was evaluated using the ACROBAT-NRSI tool. The quality of evidence relating to key outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) on health-related quality of life (HRQoL), exacerbation frequencies, COPD-related hospital admissions, and program adherence. Three independent reviewers assessed methodologic quality and reviewed the studies.

Results

Twelve randomized controlled trials (RCTs) and 2 comparative observational studies were included. While considerable evidence relating to the effectiveness of HBPR programs for COPD patients exist, overall quality is low. There were no differences between HBPR and OPR in terms of safety, HRQoL, functional exercise capacity and health care resource utilization. Compared to usual care, functional exercise capacity seemed to significantly improve after HBPR. While patient compliance with HBPR is good, two factors appeared to increase the ‘risk’ of non-compliance: expectations of patients to 1) complete daily diaries/activity logs and 2) engage in solely unsupervised exercise sessions.

Conclusion

The overall quality for most outcomes was low to very low; however, HBPR seems to offer comparable short-term benefits to OPR.
Healthcare professionals’ perspectives on facilitators of and barriers to CKD management in primary care: a qualitative study in Singapore clinics
Authors: Ramakrishnan Chandrika , Tan Ngiap Chuan , Yoon Sungwon , Hwang Sun Joon , Foo Marjorie Wai Yin , Paulpandi Muthulakshmi , Gun Shi Ying , Lee Jia Ying , Chang Zi Ying , Jafar Tazeen H.
Published: April 2022

Introduction

The burden of chronic kidney disease (CKD) is rising globally including in Singapore. Primary care is the first point of contact for most patients with early stages of CKD. However, several barriers to optimal CKD management exist. Knowing healthcare professionals’ (HCPs) perspectives is important to understand how best to strengthen CKD services in the primary care setting. Integrating a theory-based framework, we explored HCPs’ perspectives on the facilitators of and barriers to CKD management in primary care clinics in Singapore.

Methods

In-depth interviews were conducted on a purposive sample of 20 HCPs including 13 physicians, 2 nurses and 1 pharmacist from three public primary care polyclinics, and 4 nephrologists from one referral hospital. Interviews were audio recorded, transcribed verbatim and thematically analyzed underpinned by the Theoretical Domains Framework (TDF) version 2.

Results

Numerous facilitators of and barriers to CKD management identified. HCPs perceived insufficient attention is given to CKD in primary care and highlighted several barriers including knowledge and practice gaps, ineffective CKD diagnosis disclosure, limitations in decision-making for nephrology referrals, consultation time, suboptimal care coordination, and lack of CKD awareness and self-management skills among patients. Nevertheless, intensive CKD training of primary care physicians, structured CKD-care pathways, multidisciplinary team-based care, and prioritizing nephrology referrals with risk-based assessment were key facilitators. Participants underscored the importance of improving awareness and self-management skills among patients. Primary care providers expressed willingness to manage early-stage CKD as a collaborative care model with nephrologists. Our findings provide valuable insights to design targeted interventions to enhance CKD management in primary care in Singapore that may be relevant to other countries.

Conclusions

The are several roadblocks to improving CKD management in primary care settings warranting urgent attention. Foremost, CKD deserves greater priority from HCPs and health planners. Multipronged approaches should urgently address gaps in care coordination, patient-physician communication, and knowledge. Strategies could focus on intensive CKD-oriented training for primary care physicians and building novel team-based care models integrating structured CKD management, risk-based nephrology referrals coupled with education and motivational counseling for patients. Such concerted efforts are likely to improve outcomes of patients with CKD and reduce the ESKD burden.
Environmental pesticide exposure and non-Hodgkin lymphoma survival: a population-based study
Authors: Poh Christina , McPherson John D. , Tuscano Joseph , Li Qian , Parikh-Patel Arti , Vogel Christoph F. A. , Cockburn Myles , Keegan Theresa
Published: April 2022

Background

There is evidence indicating that pesticide exposure is a risk factor for non-Hodgkin lymphoma (NHL) development. However, the association between pesticide exposure and NHL survival is not well-established.

Methods

Using the California Cancer Registry, we identified patients with a first primary diagnosis of NHL from 2010 to 2016 and linked these patients with CalEnviroScreen 3.0 to obtain production agriculture pesticide exposure to 70 chemicals from the state-mandated Pesticide Use Reporting (PUR) by census tract from 2012 to 2014. In addition, data from PUR was integrated into a geographic information system that employs land-use data to estimate cumulative exposure to specific pesticides previously associated with NHL (glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4-dimethylamine salt) between 10 years prior up to 1 year after NHL diagnosis. Multivariable Cox proportional hazards regression models were used to evaluate the association between total pesticide exposure from CalEnviroScreen 3.0 and individual pesticide exposure from geographic land use data and lymphoma-specific and overall survival.

Results

Among 35,808 NHL patients identified, 44.2% were exposed to pesticide in their census tract of residence. Glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4-dimethylamine salt exposure was observed in 34.1%, 26.0%, 10.6%, 14.0%, and 12.8% of NHL patients, respectively. Total pesticide exposure at the time of diagnosis was not associated with lymphoma-specific or overall survival. In addition, no association was consistently found between glyphosate, organophosphorus, carbamate, phenoxyherbicide, and 2,4 dimethylamine salt exposure and lymphoma-specific or overall survival.

Conclusions

Although we found no consistent associations between agricultural pesticide exposure at the neighborhood level and worse survival, these results provide a platform for designing future studies to determine the association between pesticide and NHL.
A pancancer analysis of the carcinogenic role of receptor-interacting serine/threonine protein kinase-2 (RIPK2) in human tumours
Authors: Zhang Hanqun , Ma Yan , Zhang Qiuning , Liu Ruifeng , Luo Hongtao , Wang Xiaohu
Published: April 2022

Background

To explore the expression and carcinogenic mechanism of RIPK2 in human tumours, and to provide the theoretical basis for the further study of RIPK2.

Methods

We used the TCGA, CPTAC, HPA databases to analyse the expression, mutation, and prognosis of RIPK2 in human tumours. Through the Cbioportal, Ualcan, TIMER2.0, and STRING websites, We understand the genetic variation, immune infiltration and enrichment analysis of RIPK2 related genes.

Results

RIPK2 was highly expressed in most tumours (such as BRCA, COAD and LUSC, etc.), and the high expression of RIPK2 was correlated with tumour stage and prognosis. In addition, Amplification was the main type of RIPK2 in tumour mutation state, and the amplification rate was about 8.5%. In addition, RIPK2 was positively associated with tumour-infiltrating immune cells (such as CD8+ T, Tregs, and cancer-associated fibroblasts). According to the KEGG analysis, RIPK2 may play a role in tumour mainly through NOD-like signaling pathway and NF-kappaB signaling pathway. GO enrichment analysis showed that the RIPK2 is mainly related to I-kappaB kinase/NF-kappaB signaling, Ribonucleoprotein granule and Ubiquitin-like protein ligase binding.

Conclusion

RIPK2 plays an important role in the occurrence, development and prognosis of malignant tumours. Our pancancer study provided a relatively comprehensive description of the carcinogenic effects of RIPK2 in different tumours, and provided useful information for further study of RIPK2.
SARS-COV-2 as potential microRNA sponge in COVID-19 patients
Authors: Li Chang , Wang Rebecca , Wu Aurora , Yuan Tina , Song Kevin , Bai Yongsheng , Liu Xiaoming
Published: April 2022

Background

MicroRNAs (miRNAs) are a class of small non-coding RNA that can downregulate their targets by selectively binding to the 3′ untranslated region (3′UTR) of most messenger RNAs (mRNAs) in the human genome. MiRNAs can interact with other molecules such as viruses and act as a mediator for viral infection. In this study, we examined whether, and to what extent, the SARS-CoV-2 virus can serve as a “sponge” for human miRNAs.

Results

We identified multiple potential miRNA/target pairs that may be disrupted during SARS-CoV-2 infection. Using miRNA expression profiles and RNA-seq from published studies, we further identified a highly confident list of 5 miRNA/target pairs that could be disrupted by the virus’s miRNA sponge effect, namely hsa-miR-374a-5p/APOL6, hsa-let-7f-1-3p/EIF4A2, hsa-miR-374a-3p/PARP11, hsa-miR-548d-3p/PSMA2 and hsa-miR-23b-3p/ZNFX1 pairs. Using single-cell RNA-sequencing based data, we identified two important miRNAs, hsa-miR-302c-5p and hsa-miR-16-5p, to be potential virus targeting miRNAs across multiple cell types from bronchoalveolar lavage fluid samples. We further validated some of our findings using miRNA and gene enrichment analyses and the results confirmed with findings from previous studies that some of these identified miRNA/target pairs are involved in ACE2 receptor network, regulating pro-inflammatory cytokines and in immune cell maturation and differentiation.

Conclusion

Using publicly available databases and patient-related expression data, we found that acting as a “miRNA sponge” could be one explanation for SARS-CoV-2-mediated pathophysiological changes. This study provides a novel way of utilizing SARS-CoV-2 related data, with bioinformatics approaches, to help us better understand the etiology of the disease and its differential manifestation across individuals.
Gene co-expression changes underlying the functional connectomic alterations in Alzheimer’s disease
Authors: He Bing , Gorijala Priyanka , Xie Linhui , Cao Sha , Yan Jingwen
Published: April 2022

Background

There is growing evidence indicating that a number of functional connectivity networks are disrupted at each stage of the full clinical Alzheimer’s disease spectrum. Such differences are also detectable in cognitive normal (CN) carrying mutations of AD risk genes, suggesting a substantial relationship between genetics and AD-altered functional brain networks. However, direct genetic effect on functional connectivity networks has not been measured.

Methods

Leveraging existing AD functional connectivity studies collected in NeuroSynth, we performed a meta-analysis to identify two sets of brain regions: ones with altered functional connectivity in resting state network and ones without. Then with the brain-wide gene expression data in the Allen Human Brain Atlas, we applied a new biclustering method to identify a set of genes with differential co-expression patterns between these two set of brain regions.

Results

Differential co-expression analysis using biclustering method led to a subset of 38 genes which showed distinctive co-expression patterns between AD-related and non AD-related brain regions in default mode network. More specifically, we observed 4 sub-clusters with noticeable co-expression difference, where the difference in correlations is above 0.5 on average.

Conclusions

This work applies a new biclustering method to search for a subset of genes with altered co-expression patterns in AD-related default mode network regions. Compared with traditional differential expression analysis, differential co-expression analysis yielded many more significant hits with extra insights into the wiring mechanism between genes. Particularly, the differential co-expression pattern was observed between two sets of genes, suggesting potential upstream genetic regulators in AD development.
Metal ions/nucleotide coordinated nanoparticles comprehensively suppress tumor by synergizing ferroptosis with energy metabolism interference
Authors: Wang Yanqiu , Chen Jie , Lu Jianxiu , Xi Juqun , Xu Zhilong , Fan Lei , Dai Hua , Gao Lizeng
Published: April 2022

Background

Ferroptosis holds promise as a potential tumor therapy by programming cell death with a hallmark of reactive oxygen species (ROS)-induced lipid peroxidation. However, vigorous energy metabolism may assist tumors to resist oxidative damage and thus weaken the effects of ferroptosis in tumor treatment.

Results

Herein, a bifunctional antitumor platform was constructed via coordinated interactions between metal ions and nucleotides to synergistically activate ferroptosis and interrupt energy metabolism for tumor therapy. The designed nanoparticles were composed of Fe2+/small interfering RNA (siRNA) as the core and polydopamine as the cloak, which responded to the tumor microenvironment with structural dissociation, thereby permitting tumor-specific Fe2+ and siRNA release. The over-loaded Fe2+ ions in the tumor cells then triggered ferroptosis, with hallmarks of lipid peroxidation and cellular glutathione peroxidase 4 (GPX4) down-regulation. Simultaneously, the released siRNA targeted and down-regulated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in the tumor to inhibit glycolytic pathway, which interfered with tumor energy metabolism and enhanced Fe2+-induced ferroptosis to kill tumor cells.

Conclusions

This study presents a concise fabrication of a metal ion/nucleotide-based platform to integrate ferroptosis and energy metabolism intervention in one vehicle, thereby providing a promising combination modality for anticancer therapy.

Graphical Abstract
Association between quality of life and mental stress-induced myocardial ischaemia in high-risk patients after coronary revascularization
Authors: Nan Nan , Dong Wei , Gao Bingyu , Cui Feihuan , Chang Zhi , Jiao Jian , Zuo Huijuan , Mi Hongzhi , Song Xiantao , Lyu Shuzheng , Zhang Hongjia
Published: April 2022

Objective

We sought to determine the association between mental stress-induced myocardial ischaemia (MSIMI) and quality of life (QoL) in patients with coronary artery disease (CAD) after coronary revascularization.

Methods

This cohort study involved patients with high-risk MSIMI who received coronary revascularization between Dec 2018 and Dec 2019. Patients who screened positive for depression/anxiety were enrolled in this study. Mental stress was induced by the Stroop Colour and Word Test 1 month after coronary revascularization. All participants underwent single photon emission computed tomography (SPECT) scans at rest and under mental stress. MSIMI was defined as the presence of four abnormal SPECT phenomena. QoL was assessed using the Seattle Angina Questionnaire (SAQ) prior to treatment and 1 month after coronary revascularization.

Results

Of the 1845 consecutive patients who received coronary revascularization, 590 (31.9%) had depression/anxiety, and 205 agreed to accept the mental stress test. During the average observation period of 33 days, 105 (51.2%) patients exhibited MSIMI. All SAQ subscales showed significant improvement, except for QoL, in the MSIMI group. The QoL score was lower (− 0.2 ± 32.7 vs. 13.1 ± 29.9, P = 0.005), and the proportion of deterioration in QoL was higher (50.5% vs. 31.9%, P = 0.010) in the MSIMI group than in the non-MSIMI group. Those with a deterioration in QoL had approximately twice the rate of MSIMI than those with an improvement in QoL (unadjusted OR: 2.019, 95% CI 1.122–3.634, P = 0.026; adjusted OR: 1.968, 95% CI 1.083–3.578, P = 0.017).

Conclusion

Among patients with CAD who received coronary revascularization and had depression/anxiety, deterioration in QoL increased the likelihood of MSIMI. Hence, our results indicate that deterioration in QoL is a predictor of MSIMI.

Trail Registration ChiCTR2200055792, retrospectively registered, 2022.1.20, www.medresman.org.cn
A seven-autophagy-related gene signature for predicting the prognosis of differentiated thyroid carcinoma
Authors: Li Chengxin , Yuan Qianqian , Xu Gaoran , Yang Qian , Hou Jinxuan , Zheng Lewei , Wu Gaosong
Published: April 2022

Background

Numerous studies have implicated autophagy in the pathogenesis of thyroid carcinoma. This investigation aimed to establish an autophagy-related gene model and nomogram that can help predict the overall survival (OS) of patients with differentiated thyroid carcinoma (DTHCA).

Methods

Clinical characteristics and RNA-seq expression data from TCGA (The Cancer Genome Atlas) were used in the study. We also downloaded autophagy-related genes (ARGs) from the Gene Set Enrichment Analysis website and the Human Autophagy Database. First, we assigned patients into training and testing groups. R software was applied to identify differentially expressed ARGs for further construction of a protein-protein interaction (PPI) network for gene functional analyses. A risk score-based prognostic risk model was subsequently developed using univariate Cox regression and LASSO-penalized Cox regression analyses. The model’s performance was verified using Kaplan-Meier (KM) survival analysis and ROC curve. Finally, a nomogram was constructed for clinical application in evaluating the patients with DTHCA. Finally, a 7-gene prognostic risk model was developed based on gene set enrichment analysis.

Results

Overall, we identified 54 differentially expressed ARGs in patients with DTHCA. A new gene risk model based on 7-ARGs (CDKN2A, FGF7, CTSB, HAP1, DAPK2, DNAJB1, and ITPR1) was developed in the training group and validated in the testing group. The predictive accuracy of the model was reflected by the area under the ROC curve (AUC) values. Univariate and multivariate Cox regression analysis indicated that the model could independently predict the prognosis of patients with THCA. The constrained nomogram derived from the risk score and age also showed high prediction accuracy.

Conclusions

Here, we developed a 7-ARG prognostic risk model and nomogram for differentiated thyroid carcinoma patients that can guide clinical decisions and individualized therapy.
Significance of fibulin-3 expression in bladder cancer: a tissue microarray-based immunohistochemical study
Authors: Al Khader Ali , Fararjeh Abdul Fattah S. , Kaddumi Ezidin G. , Al-Saghbini Mohamad
Published: April 2022

Background

Predicting the behavior of bladder cancer by easy noninvasive methods and with less cost is needed. Fibulin-3 (EFEMP1), a glycoprotein of the extracellular matrix that is encoded by the gene EFEMP1, has been nominated as one of the potential mediators of muscle invasion in bladder cancer.

Methods

In this tissue microarray-based immunohistochemical study, fibulin-3 level of expression was evaluated using a semiquantitative scoring system and was correlated with patient’s age and sex and tumor grade and stage.

Results

A total of 160 urothelial carcinoma cases were analyzed. The age of the patients ranged from 25 to 91 years (mean, 60.15; SD, 11.60). Fibulin-3 was significantly associated with muscle invasion and overall tumor stage (p = 0.033 and 0.02, respectively). Fibulin-3 expression was nonsignificantly associated with tumor grade (p = 0.092)

Conclusions

We found that the expression of fibulin-3 is significantly associated with muscle invasion in urinary bladder urothelial carcinoma. However, the prognostic role of fibulin-3 needs further investigations.
Increased testicular insulin-like growth factor 1 is associated with gonadal activation by recombinant growth hormone in immature rats
Authors: Xu Yang , Han Chang Yong , Park Mi Jung , Gye Myung Chan
Published: April 2022

Background

In children, recombinant human growth hormone (rhGH) therapy for treatment of short stature has raised concerns of the early onset of puberty. Puberty is initiated by the activation of the hypothalamus-pituitary-gonad axis. Insulin-like growth factor-1 (IGF1) has been known to mediate physiologic effects of GH. To understand the mechanism of precocious sexual maturation following prepubertal GH therapy, the effects of rhGH on the hypothalamus-pituitary-gonad axis were examined in the immature male rats.

Methods

Immature male rats were given by daily injection of rhGH (1 or 2 IU/kg) from postnatal day (PND) 21 to PND 23 or 30. The effects of rhGH on kisspeptin-GnRH-LH system in the hypothalamus-pituitary axis, systemic and testicular IGF1, spermatogenesis, steroidogenesis, and circulating testosterone levels were examined. The effects of rhGH on the IGF1 expression and steroidogenesis were examined in progenitor LCsin vitro.

Results

Testicular steroidogenic pathway and spermatogenesis marker mRNA levels, number and size of 17β-hydroxysteroid dehydrogenase (+) LCs, and blood testosterone levels of rhGH rats were significantly higher than those of controls on PNDs 24 and 31. HypothalamicKiss1andGnrh1mRNA of rhGH rats were significantly higher than those of controls on PND 24, indicating early activation of hypothalamic kisspeptin-GnRH neurons by rhGH. HypothalamicIgf1mRNA levels of rhGH rats were significantly higher than those of controls on PND 24 but significantly lower than those of controls on PND 31. TesticularIgf1mRNA levels were significantly higher in rhGH rats than in the controls on PNDs 24 and 31 whereas circulating IGF1 levels were not. In progenitor LCs, rhGH significantly increasedIgf1and steroidogenic pathway mRNA levels and testosterone production.

Conclusions

Local increases in testicular IGF1 might be an important mediator of gonadal maturation via activation of LCs steroidogenesis in immature rats given rhGH.
Practitioners’ perspectives on family-based intervention for illicit drug-using adolescents in Taiwan: a qualitative study
Authors: Huang Lanying
Published: April 2022

Background

Drug-related psychiatric comorbidity or death among adolescents has grown to become a public health threat in Taiwan. In an atmosphere of abstinence, few alternatives or rehabilitative options for troubled young people have caused many juveniles to be driven away from home and placed in closed institutions. The intersectionality of illegal substance use, deviant behaviours, and criminal offences among adjudicated adolescents is a challenge for the development of adolescent users’ harm reduction strategies. In addition, the relationships among the adolescents, their families, and practitioners might be undermined by coercive and mandatory court measures. As developing a harm reduction approach includes minimizing the negative effects on not only adolescents and also their families, this study aims to explore Taiwanese practitioners’ perspectives of family-based programmes for drug-using adolescents.

Methods

This study adopted a qualitative approach. Through face-to-face interviews and a focus group, accounts were collected from 28 key informants working in youth delinquency. The interviews were transcribed for analysis using qualitative analysis software, namely NVivo10.

Results

Practitioners tend to refer to an “adolescent-centred model” when describing their work with drug-using young people. From the frontline practitioners’ descriptions, the families of those youth needing treatment services are often vulnerable and disadvantaged. These families are seldom onboard because of low readiness and scarce resources. Although a legal framework is in place, resources, workforce, and programmes to engage and involve parents in the intervention are lacking. Despite the obstacles, practitioners have utilized a variety of strategies to obtain limited success, such as parent meetings, resources referrals, parent counselling, court support, voluntary parenting courses, illicit substance information sharing, and home visits. Practitioners also pointed out that therapeutic interventions are more effective than coercive or mandatory interventions for adolescents and also for their families.

Conclusions

Since most practitioners have an adolescent-centred work principle, their work with parents falls into professional-centred or family-allied work models. It is therefore suggested that resources be reallocated to involve parent counselling and intense treatment instead of mandatory parental education.
Semi-prone thoracoscopic esophagectomy for esophageal carcinoma with aberrant right subclavian artery and non-recurrent inferior laryngeal nerve
Authors: Koyama Kazunori , Watanabe Toru , Kato Hideaki , Kawaguchi Masahiko
Published: April 2022

Background

Aberrant right subclavian artery (ARSA) accompanied by non-recurrent inferior laryngeal nerve (NRILN) is a rare anomaly. In cases of thoracic esophageal carcinoma associated with ARSA and NRILN, surgeons must take extra care not to injury these vessels and nerves. We believe semi-prone thoracoscopic esophagectomy to be a surgical approach that can safely deal with such an anomaly.

Case presentation

A 70-year-old man complained of feelings of chest constriction. Endoscopic examination revealed an esophageal tumor and computed tomography showed an ARSA. We performed semi-prone thoracoscopic esophagectomy for case with ARSA and NRILN. We identified these anomalies during esophagectomy, and we could complete surgery without injury these vessels and nerves. The patient had an uneventful recovery and discharged 22 days after surgery.

Conclusions

Semi-prone thoracoscopic esophagectomy for esophageal carcinoma can be performed safely with a wide operative field, and is an excellent procedure for dissecting esophageal carcinoma in patients with ARSA and NRILN.
Trauma-focused treatments for refugee children: study protocol for a randomized controlled trial of the effectiveness of KIDNET versus EMDR therapy versus a waitlist control group (KIEM)
Authors: Velu Merel E. , Martens Irene , Shahab Mona , de Roos Carlijn , Jongedijk Ruud A. , Schok Michaela , Mooren T.
Published: April 2022

Background

Prevalence of posttraumatic stress disorder (PTSD) in refugees is reportedly higher in comparison to the general population. Refugee children specifically are often coping with trauma and loss and are at risk for mental health difficulties. With staggering numbers of people seeking refuge around the world and 50% being 18 years or younger, research examining the effects of trauma-focused therapies for refugee children with PTSD is highly needed. Both Eye Movement Desensitization and Reprocessing (EMDR) therapy and the child version of Narrative Exposure Therapy (KIDNET) have been used for refugees, although these treatment methods have not been systematically compared. The aim of the current study is to investigate the effectiveness of EMDR and KIDNET, compared to a waitlist control group and with each other, offered to refugee children.

Methods

A randomized controlled three-arm trial has been designed. The primary outcome is PTSD diagnosis and symptom severity assessed with the Clinician-Administered PTSD Scale for Children DSM5 (CAPS-CA-5) at baseline (T1), 1 month post-treatment, or after 8 weeks of waiting (T2) and 3 months follow-up (T3). Additionally, instruments to assess posttraumatic stress symptoms, behavioral and emotional problems, and quality of life perception in children aged 8–18 are conducted at T1, T2, and T3.

Discussion

This is the first RCT that examines the effectiveness of EMDR and KIDNET in refugee children aged 8–18 years specifically, compared to a waitlist control group intended to reduce PTSD diagnosis and severity of posttraumatic stress symptoms and comorbid complaints in a growing and challenging population.

Trial registration

Dutch Trial Register NL40769. Retrospectively registered on June 16, 2021.
An adaptive design to screen, treat, and retain people with opioid use disorders who use methamphetamine in methadone clinics (STAR-OM): study protocol of a clinical trial
Authors: Giang Le Minh , Trang Nguyen Thu , Diep Nguyen Bich , Thuy Dao Thi Dieu , Thuy Dinh Thanh , Hoe Han Dinh , Van Hoang Thi Hai , Truc Thai Thanh , Nguyen Hoa H. , Lai Nguyen Ly , Linh Pham Thi Dan , Vi Vu Thi Tuong , Reback Cathy J. , Leibowitz Arleen , Li Li , Lin Chunqing , Li Michael , Do Van Dung  , Shoptaw Steve
Published: April 2022

Background

Methamphetamine use could jeopardize the current efforts to address opioid use disorder and HIV infection. Evidence-based behavioral interventions (EBI) are effective in reducing methamphetamine use. However, evidence on optimal combinations of EBI is limited. This protocol presents a type-1 effectiveness-implementation hybrid design to evaluate the effectiveness, cost-effectiveness of adaptive methamphetamine use interventions, and their implementation barriers in Vietnam.

Method

Design: Participants will be first randomized into two frontline interventions for 12 weeks. They will then be placed or randomized to three adaptive strategies for another 12 weeks. An economic evaluation and an ethnographic evaluation will be conducted alongside the interventions.

Participants: We will recruit 600 participants in 20 methadone clinics. Eligibility criteria: (1) age 16+; (2) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores ≥ 10 for methamphetamine use or confirmed methamphetamine use with urine drug screening; (3) willing to provide three pieces of contact information; and (4) having a cell phone.

Outcomes: Outcomes are measured at 13, 26, and 49 weeks and throughout the interventions. Primary outcomes include the (1) increase in HIV viral suppression, (2) reduction in HIV risk behaviors, and (3) reduction in methamphetamine use.

COVID-19 response: We developed a response plan for interruptions caused by COVID-19 lockdowns to ensure data quality and intervention fidelity.

Discussion

This study will provide important evidence for scale-up of EBIs for methamphetamine use among methadone patients in limited-resource settings. As the EBIs will be delivered by methadone providers, they can be readily implemented if the trial demonstrates effectiveness and cost-effectiveness.

Trial registration

ClinicalTrials.gov NCT04706624. Registered on 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624
The effect of a social network-based cognitive behavioral therapy intervention on the severity of premenstrual syndrome symptoms: a protocol of a randomized clinical trial study
Authors: Alimoradi Zainab , Rajabalipour Somayeh , Rahmani Khaled , Pakpour Amir H.
Published: April 2022

Background

Premenstrual syndrome (PMS) is one of the most widespread menstrual disorders in women of reproductive age. This recurrent syndrome is a combination of physically, mentally, or behaviorally disturbing changes occurring during the secretory phase of the menstrual cycle. The aim of this study is to determine the effect of a cognitive-behavioral therapy-based educational intervention using social networks on PMS in female health center employees in Rudbar, Iran.

Methods/design

A randomized superiority controlled trial will be conducted involving 140 female employees of health centers affiliated with the Guilan University of Medical Sciences, Rudbar. The study involves a block size of 4 and 6 in a randomly varied order, 140 women who meet all the inclusion criteria will be randomly and equally divided into 2 groups: the intervention and the control groups. Those in the former group will receive a cognitive-behavioral therapy-based treatment for eight consecutive weeks on the social network platform WhatsApp; however, those in the control group will not be offered any treatment except usual care practices (unprotocolized usual care). The study’s primary outcome is the severity of PMS symptoms, and the secondary outcomes include general self-efficacy, work-related quality of life, the impact of PMS on daily life, coping with the symptoms, and experiencing anxiety and depression at the beginning of the study to identify people with PMS. A daily record of the symptoms will be completed for two consecutive months by all female employees aged 20–45 years who wish to participate in the study. According to the initial screening, those with moderate to severe PMS will be included. We will use the MLwin software for the analyses. All questionnaires will be completed by both groups immediately and 8 weeks after the termination of the treatment. The data will be analyzed using linear mixed-effects modeling with random intercepts and slopes.

Discussion

It is anticipated that the findings of the present study may demonstrate the effectiveness of the cognitive behavioral therapy intervention on the severity of PMS symptoms that could guide healthcare providers in opting for suitable treatment alternatives for the syndrome.

Ethics and dissemination

The research proposal is approved by the Human Ethics Committee of Qazvin University of Medical Sciences (IR.QUMS.REC.1399.252). The results of this intervention trial will be submitted for publication in a peer-reviewed research journal.

Trial registration

Iranian Registry of Clinical Trials IRCT20180218038789N4. Registered prospectively on October 28, 2020
Health effects of utilising hospital contacts to provide measles vaccination to children 9–59 months—a randomised controlled trial in Guinea-Bissau
Authors: Fisker Ane B. , Martins Justiniano S. D. , Jensen Andreas M. , Martins Cesario , Aaby Peter , Thysen Sanne M.
Published: April 2022

Background

Measles vaccination coverage in Guinea-Bissau is low; fewer than 80% of children are currently measles vaccinated before 12 months of age. The low coverage hampers control of measles. Furthermore, accumulating evidence indicates that measles vaccine has beneficial non-specific effects, strengthening the resistance towards other infections. Thus, even if children are not exposed to measles virus, measles-unvaccinated children may be worse off. To increase vaccination coverage, WHO recommends that contacts with the health system for mild illness are utilised to vaccinate. Currently, in Guinea-Bissau, curative health system contacts are not utilised.

Methods

Bandim Health Project registers out-patient consultations and admissions at the paediatric ward of the National Hospital in Guinea-Bissau. Measles-unvaccinated children aged 9–59 months consulting for milder illness or being discharged from the paediatric ward will be invited to participate in a randomised trial. Among 5400 children, randomised 1:1 to receive standard measles vaccine or a saline placebo, we will test the hypothesis that providing a measles vaccine at discharge lowers the risk of admission/mortality (composite outcome) during the subsequent 6 months by 25%. All enrolled children are followed through the Bandim Health Project registration system and through telephone follow-up. The first 1000 enrolled children are furthermore followed through interviews on days 2, 4, 7 and 14 after enrolment.

Discussion

Utilising missed vaccination opportunities can increase vaccination coverage and may improve child health. However, without further evidence for the safety and potential benefits of measles vaccination, these curative contacts are unlikely to be used for vaccination in Guinea-Bissau.

Trial registration

www.ClinicalTrials.gov NCT04220671. Registered on 5 January 2020.
Clinical implementation of an algorithm for predicting exacerbations in patients with COPD in telemonitoring: a study protocol for a single-blinded randomized controlled trial
Authors: Secher Pernille Heyckendorff , Hangaard Stine , Kronborg Thomas , Hæsum Lisa Korsbakke Emtekær , Udsen Flemming Witt , Hejlesen Ole , Bender Clara
Published: April 2022

Background

Acute exacerbations have a significant impact on patients with COPD by accelerating the decline in lung function leading to decreased health-related quality of life and survival time. In telehealth, health care professionals exercise clinical judgment over a physical distance. Telehealth has been implemented as a way to monitor patients more closely in daily life with an intention to intervene earlier when physical measurements indicate that health deteriorates. Several studies call for research investigating the ability of telehealth to automatically flag risk of exacerbations by applying the physical measurements that are collected as part of the monitoring routines to support health care professionals. However, more research is needed to further develop, test, and validate prediction algorithms to ensure that these algorithms improve outcomes before they are widely implemented in practice.

Method

This trial tests a COPD prediction algorithm that is integrated into an existing telehealth system, which has been developed from the previous Danish large-scale trial, TeleCare North (NCT: 01984840). The COPD prediction algorithm aims to support clinical decisions by predicting the risk of exacerbations for patients with COPD based on selected physiological parameters. A prospective, parallel two-armed randomized controlled trial with approximately 200 participants with COPD will be conducted. The participants live in Aalborg municipality, which is located in the North Denmark Region. All participants are familiar with the telehealth system in advance. In addition to the participants’ usual weekly monitored measurements, they are asked to measure their oxygen saturation two more times a week during the trial period. The primary outcome is the number of exacerbations defined as an acute hospitalization from baseline to follow-up. Secondary outcomes include changes in health-related quality of life measured by both the 12-Item Short Form Survey version 2 and EuroQol-5 Dimension Questionnaire as well as the incremental cost-effectiveness ratio.

Discussion

This trial seeks to explore whether the COPD prediction algorithm has the potential to support early detection of exacerbations in a telehealth setting. The COPD prediction algorithm may initiate timely treatment, which may decrease the number of hospitalizations.

Trial registration

NCT05218525 (pending at clinicaltrials.gov) (date, month, year)