bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges to ensuring valid and useful waiting time monitoring – a qualitative study in Swedish specialist care
Authors: Ebbevi David , Hasson Henna , Lönnroth Knut , Augustsson Hanna
Published: September 2021

Background

Access to health care is an essential health policy issue. In several countries, waiting time guarantees mandate set time limits for assessment and treatment. High-quality waiting time data are necessary to evaluate and improve waiting times. This study’s aim was to investigate health care providers and administrative management professionals’ perceptions of validity and usefulness of waiting time reporting in specialist care.

Methods

Semi-structured interviews (n = 28) were conducted with administrative management and care professionals (line managers and care providers) in specialized clinics in the Stockholm Region, Sweden. Clinic-specific data from the waiting time registry was used in the care provider interviews to assess face validity. Clinics were purposefully sampled for maximum variation in complexity of care, volume of production, geographical location, private or public ownership, and local waiting times. Thematic analysis was used.

Results

The waiting time registry was perceived to have low validity and usefulness. Perceived validity and usefulness were interconnected, with mechanisms that reinforced the connection. Structural and cognitive barriers to validity included technical and procedural errors, errors caused by role division, misinterpretation of guidelines, diverging interpretations of nonregulated cases and extensive willful manipulation of data.

Conclusions

We identify four misconceptions underpinning the current waiting time reporting system: passive dissemination of guidelines is sufficient as implemented, cognitive load of care providers to report waiting times is negligible, soft-law regulation and presentation of outcome data is sufficient to drive improvement, and self-reported data linked to incentives poses a low risk of data corruption. To counter low validity and usefulness, we propose the following for policy makers and administrative management when developing and implementing waiting time monitoring: communicate guidelines with instructions for operationalization, address barriers to implementation, ensure quality through monitoring of implementation and adherence to guidelines, develop IT ontology together with professionals, avoid parallel measurement infrastructures, ensure waiting times are presented to suit management needs, provide timely waiting time data, enable the study of single cases, minimize manual data entry, and perform spot-checks or external validity checks. Several of these strategies should be transferable to waiting time monitoring in other contexts.
Driving factors for the utilisation of healthcare services by people with osteoarthritis in Portugal: results from a nationwide population-based study
Authors: Costa Daniela , Rodrigues Ana M. , Cruz Eduardo B. , Canhão Helena , Branco Jaime , Nunes Carla
Published: September 2021

Background

Worldwide, the current management of knee osteoarthritis appears heterogeneous, high-cost and often not based on current best evidence. The absence of epidemiological data regarding the utilisation of healthcare services may conceal the need for improvements in the management of osteoarthritis. The aim of this study is to explore the profiles of healthcare services utilisation by people with knee osteoarthritis, and to analyse their determinants, according to Andersen’s behavioural model.

Methods

We analysed a sample of 978 participants diagnosed with knee osteoarthritis from the population-based study EpiReumaPt, in Portugal. Data was collected with a structured interview, and the diagnosis of knee osteoarthritis was validated by a rheumatologist team. With the Two-step Cluster procedure, we primarily identified different profiles of healthcare utilisation according to the services most used by patients with knee osteoarthritis. Secondly, we analysed the determinants of each profile, using multinomial logistic regression, according to the predisposing characteristics, enabling factors and need variables.

Results

In our sample, a high proportion of participants are overweight or obese (82,6%, n = 748) and physically inactive (20,6%, n = 201) and a small proportion had physiotherapy management (14,4%, n = 141). We identified three profiles of healthcare utilisation: “HighUsers”; “GPUsers”; “LowUsers”. “HighUsers” represents more than 35% of the sample, and are also the participants with higher utilisation of medical appointments. “GPUsers” represent the participants with higher utilisation of general practitioner appointments. Within these profiles, age and geographic location – indicated as predisposing characteristics; employment status and healthcare insurance - as enabling factors; number of comorbidities, physical function, health-related quality of life, anxiety and physical exercise - as need variables, showed associations (p < 0,05) with the higher utilisation of healthcare services profiles.

Conclusions

Healthcare utilisation by people with knee osteoarthritis is not driven only by clinical needs. The predisposing characteristics and enabling factors associated with healthcare utilisation reveal inequities in the access to healthcare and variability in the management of people with knee osteoarthritis. Research and implementation of whole-system strategies to improve equity in the access and quality of care are paramount in order to diminish the impact of osteoarthritis at individual-, societal- and economic-level.
Association of multimorbidity and changes in health-related quality of life following myocardial infarction: a UK multicentre longitudinal patient-reported outcomes study
Authors: Munyombwe T. , Dondo T. B. , Aktaa S. , Wilkinson C. , Hall M. , Hurdus B. , Oliver G. , West R. M. , Hall A. S. , Gale C. P.
Published: September 2021

Background

Multimorbidity is prevalent for people with myocardial infarction (MI), yet previous studies investigated single-health conditions in isolation. We identified patterns of multimorbidity in MI survivors and their associations with changes in HRQoL.

Methods

In this national longitudinal cohort study, we analysed data from 9566 admissions with MI from 77 National Health Service hospitals in England between 2011 and 2015. HRQoL was measured using EuroQol 5 dimension (EQ5D) instrument and visual analogue scale (EQVAS) at hospitalisation, 6, and 12 months following MI. Latent class analysis (LCA) of pre-existing long-term health conditions at baseline was used to identify clusters of multimorbidity and associations with changes in HRQoL quantified using mixed effects regression analysis.

Results

Of 9566 admissions with MI (mean age of 64.1 years [SD 11.9], 7154 [75%] men), over half (5119 [53.5%] had multimorbidities. LCA identified 3 multimorbidity clusters which were severe multimorbidity (591; 6.5%) with low HRQoL at baseline (EQVAS 59.39 and EQ5D 0.62) which did not improve significantly at 6 months (EQVAS 59.92, EQ5D 0.60); moderate multimorbidity (4301; 47.6%) with medium HRQoL at baseline (EQVAS 63.08, EQ5D 0.71) and who improved at 6 months (EQVAS 71.38, EQ5D 0.76); and mild multimorbidity (4147, 45.9%) at baseline (EQVAS 64.57, EQ5D 0.75) and improved at 6 months (EQVAS 76.39, EQ5D 0.82). Patients in the severe and moderate groups were more likely to be older, women, and presented with NSTEMI. Compared with the mild group, increased multimorbidity was associated with lower EQ-VAS scores (adjusted coefficient: −5.12 [95% CI −7.04 to −3.19] and −0.98 [−1.93 to −0.04] for severe and moderate multimorbidity, respectively.

The severe class was more likely than the mild class to report problems in mobility, OR 9.62 (95% confidence interval: 6.44 to 14.36), self-care 7.87 (4.78 to 12.97), activities 2.41 (1.79 to 3.26), pain 2.04 (1.50 to 2.77), and anxiety/depression 1.97 (1.42 to 2.74).

Conclusions

Among MI survivors, multimorbidity clustered into three distinct patterns and was inversely associated with HRQoL. The identified multimorbidity patterns and HRQoL domains that are mostly affected may help to identify patients at risk of poor HRQoL for which clinical interventions could be beneficial to improve the HRQoL of MI survivors.

Trial registration

ClinicalTrials.govNCT01808027andNCT01819103
The association of hepatic steatosis and fibrosis with heart failure and mortality
Authors: Park Jiyun , Kim Gyuri , Kim Hasung , Lee Jungkuk , Lee You-Bin , Jin Sang-Man , Hur Kyu Yeon , Kim Jae Hyeon
Published: September 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic disease and independently affects the development of cardiovascular (CV) disease. We investigated whether hepatic steatosis and/or fibrosis are associated with the development of incident heart failure (iHF), hospitalized HF (hHF), mortality, and CV death in both the general population and HF patients.

Methods

We analyzed 778,739 individuals without HF and 7445 patients with pre-existing HF aged 40 to 80 years who underwent a national health check-up from January 2009 to December 2012. The presence of hepatic steatosis and advanced hepatic fibrosis was determined using cutoff values for fatty liver index (FLI) and BARD score. We evaluated the association of FLI or BARD score with the development of iHF, hHF, mortality and CV death using multivariable-adjusted Cox regression models.

Results

A total of 28,524 (3.7%) individuals in the general population and 1422 (19.1%) pre-existing HF patients developed iHF and hHF respectively. In the multivariable-adjusted model, participants with an FLI ≥ 60 were at increased risk for iHF (hazard ratio [HR], 95% confidence interval [CI], 1.30, 1.24–1.36), hHF (HR 1.54, 95% CI 1.44–1.66), all-cause mortality (HR 1.62, 95% CI 1.54–1.70), and CV mortality (HR 1.41 95% CI 1.22–1.63) in the general population and hHF (HR 1.26, 95% CI 1.21–1.54) and all-cause mortality (HR 1.54 95% CI 1.24–1.92) in the HF patient group compared with an FLI < 20. Among participants with NAFLD, advanced liver fibrosis was associated with increased risk for iHF, hHF, and all-cause mortality in the general population and all-cause mortality and CV mortality in the HF patient group (all p < 0.05).

Conclusion

Hepatic steatosis and/or advanced fibrosis as assessed by FLI and BARD score was significantly associated with the risk of HF and mortality.
Dynamic serum biomarkers to predict the efficacy of PD-1 in patients with nasopharyngeal carcinoma
Authors: Zhang Ao , Zhong Guanqing , Wang Luocan , Cai Rongzeng , Han Runkun , Xu Caixia , Chen Shulin , Sun Peng , Chen Hao
Published: September 2021

Background

There is a lack of effective treatments for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). Furthermore, the response rate of NPC patients to programmed death 1 (PD-1) inhibitors is approximately 20% to 30%. Thus, we aimed to explore reliable and minimally invasive prognostic indicators to predict the efficacy of PD-1 inhibitors combination therapy in RM-NPC.

Methods

The serum markers of 160 RM-NPC patients were measured before and three weeks after the first anti-PD-1 treatment. The least absolute shrinkage and selection operator (LASSO) logistic regression was carried out to select dynamic serum indicators and construct a prediction model. Furthermore, we carried out univariate, multivariate, nomogram and survival analyses to identify independent prognostic factors that were associated with 1-year progression-free survival (PFS).

Results

Based on two markers that were screened by Lasso logistic regression, we constructed a risk score prediction model for the prediction of anti-PD-1 efficacy at 8–12 weeks with an AUC of 0.737 in the training cohort and 0.723 in the validation cohort. Risk score and metastases were included in the nomogram, and the Kaplan–Meier survival curves demonstrated that the high-risk group has shorter PFS compared to the low-risk group. The concordance index (C-index) of the nomogram for PFS is higher than that of the TNM stage in the training and validation cohort.

Conclusion

We proposed a strategy to monitor dynamic changes in the biochemistry markers and emphasized their importance as potential prognostic biomarkers for the treatment of advanced NPC treated with PD-1 inhibitors. Our risk score prediction model was based on the dynamic change of LDH and AST/ALT, which has predictive and prognostic value for NPC patients who were treated with PD-1 inhibitors.
Echocardiographic assessment of diastolic dysfunction in elderly patients with severe aortic stenosis before and after aortic valve replacement
Authors: Caglayan Hatice Akay , Kjønås Didrik , Malm Siri , Schirmer Henrik , Rösner Assami
Published: September 2021

Background

The 2016 guidelines of the American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) for evaluation of left ventricular (LV) diastolic dysfunction by Doppler flow and tissue Doppler- echocardiography do not adjust assessment of high filling pressures for patients with aortic stenosis (AS). However, most of the studies on this patient group indicate age independent specific diastolic features in AS. The aim of this study is to identify disease-specific range and distribution of diastolic functional parameters and their ability to identify high N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels as a marker for high filling pressures.

Methods

In this study, 169 patients who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Resting echocardiography was performed including Doppler of the mitral inflow, pulmonary venous flow, tricuspid regurgitant flow and tissue Doppler in the mitral ring and indexed volume-estimates of the left atrium (LAVI). Echocardiography, and NT-proBNP levels were assessed before TAVR/SAVR and at two postoperative visits at 6 and 12 months.

Results

Pre- and postoperative values were septal e′; 5.1 ± 3.9, 5.2 ± 1.6 cm/s; lateral e′ 6.3 ± 2.1; 7.7 ± 2.7 cm/s; E/e′19 ± 8; 16 ± 7 cm/s; E velocity 96 ± 32; 95 ± 32 cm/s; LAVI 39 ± 8; 36 ± 8 ml/m2, pulmonary artery pressure (PAP) 39 ± 8; 36 ± 8 mmHg, respectively. The scoring recommended by ASE/EACVI detected elevated NT pro-BNP with a specificity of 25%. Adjusting thresholds towards PAP ≥ 40 mmHg, E velocity ≥ 100 cm/s, E deceleration time < 220 ms, and E/septal e′ ≥ 20 or septal e′ < 5.0 cm/s increased prediction of NT-proBNP levels ≥500 ng/L with substantially improved specificity (> 85%).

Conclusion

Diastolic echocardiographic parameters in AS indicate persistent impaired relaxation and NT-proBNP indicate elevated filling pressures in most of the patients, improving only modestly 6–12 months after TAVR and SAVR. Applying the 2016 ASE/EACVI recommendations for detection of elevated filling pressures to patients with AS, elevated NT pro-BNP levels could not be reliably detected. However, adjusting thresholds of the echocardiographic parameters increased specificities to useful diagnostic levels.

Trial registration

The study was prospectively approved by the regional ethical committee, REK North with the registration number: REK 2010/397-10.
Metabolic labeling of enterovirus 71 with quantum dots for the study of virus receptor usage
Authors: Ke Xianliang , Li Chunjie , Luo Dan , Wang Ting , Liu Yan , Tan Zhongyuan , Du Mingyuan , He Zhike , Wang Hanzhong , Zheng Zhenhua , Zhang Yuan
Published: September 2021

Fluorescent labeling and dynamic tracking is a powerful tool for exploring virus infection mechanisms. However, for small-sized viruses, virus tracking studies are usually hindered by a lack of appropriate labeling methods that do not dampen virus yield or infectivity. Here, we report a universal strategy for labeling viruses with chemical dyes and Quantum dots (QDs). Enterovirus 71 (EV71) was produced in a cell line that stably expresses a mutant methionyl-tRNA synthetase (MetRS), which can charge azidonorleucine (ANL) to the methionine sites of viral proteins during translation. Then, the ANL-containing virus was easily labeled with DBCO-AF647 and DBCO-QDs. The labeled virus shows sufficient yield and no obvious decrease in infectivity and can be used for imaging the virus entry process. Using the labeled EV71, different functions of scavenger receptor class B, member 2 (SCARB2), and heparan sulfate (HS) in EV71 infection were comparatively studied. The cell entry process of a strong HS-binding EV71 strain was investigated by real-time dynamic visualization of EV71-QDs in living cells. Taken together, our study described a universal biocompatible virus labeling method, visualized the dynamic viral entry process, and reported details of the receptor usage of EV71.

Graphic Abstract
An atherosclerotic plaque-targeted single-chain antibody for MR/NIR-II imaging of atherosclerosis and anti-atherosclerosis therapy
Authors: Zhang Liwei , Xue Sheng , Ren Feng , Huang Siyang , Zhou Ruizhi , Wang Yu , Zhou Changyong , Li Zhen
Published: September 2021

Background

Oxidation-specific epitopes (OSEs) are rich in atherosclerotic plaques. Innate and adaptive immune responses to OSEs play an important role in atherosclerosis. The purpose of this study was to develop novel human single-chain variable fragment (scFv) antibody specific to OSEs to image and inhibit atherosclerosis.

Results

Here, we screened a novel scFv antibody, named as ASA6, from phage-displayed human scFv library. ASA6 can bind to oxidized LDL (Ox-LDL) and atherosclerotic plaques. Meanwhile, ASA6 can also inhibit the uptake of Ox-LDL into macrophage to reduce macrophage apoptosis. The atherosclerotic lesion area ofApoE−/−mice administrated with ASA6 antibody was significantly reduced. Transcriptome analysis reveals the anti-atherosclerosis effect of ASA6 is related to the regulation of fatty acid metabolism and inhibition of M1 macrophage polarization. Moreover, we conjugated ASA6 antibody to NaNdF4@NaGdF4nanoparticles for noninvasive imaging of atherosclerotic plaques by magnetic resonance (MR) and near-infrared window II (NIR-II) imaging.

Conclusions

Together, these data demonstrate the potential of ASA6 antibody in targeted therapy and noninvasive imaging for atherosclerosis.

Graphic abstract
No impact of Asian ethnicity on EORTC QLQ-C30 scores: Group differences and differential item functioning in paroxysmal nocturnal hemoglobinuria
Authors: Schwartz Carolyn E. , Stark Roland B. , Borowiec Katrina , Myren Karl-Johan
Published: September 2021

Background

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening terminal-complement-mediated disease resulting in intravascular hemolysis and thrombosis with significant morbidity and premature mortality. There exists no disease-specific quality-of-life (QOL) measure for PNH. Its QOL effects resemble those of hematologic cancers, which supports the use of cancer-specific QOL measures in PNH clinical trials. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 has published norms for many European and North American countries, but not for Asian countries. We investigated differences by Asian ethnicity in scores and item function on the EORTC QLQ-C30.

Methods

This secondary analysis focused on two non-inferiority PNH trials (301 and 302) comparing eculizumab and ravulizumab (n = 441). Analysis of covariance examined the main effect of Asian ethnicity on baseline EORTC QLQ-C30 scores, after adjusting for propensity scores encompassing trial, demographic and clinical factors. Mixed modeling of longitudinal data compared subscale scores in Asian vs. non-Asian patients, after propensity adjustment. Differential item function (DIF) was examined using ordinal regression models at baseline and longitudinally, to predict item score from total score, ethnicity, and their interaction to test for uniform DIF (significant main effect for Asian) and non-uniform DIF (significant Asian-by-total-score interaction).

Results

Of the 15 baseline domains, Asian patients scored slightly better on role and emotional functioning and slightly worse on constipation and diarrhea (0.22 < Cohen’s d < 0.36). In longitudinal models, Asians reported slightly higher appetite loss, diarrhea, and financial difficulties than non-Asians (R2 increment < 0.0005). There was negligible uniform and non-uniform DIF, i.e., R2 0 to 0.018, far below Zumbo’s (1999) criterion of 0.13. On average there were larger differences from norms for Asians (mean = 0.05, sd = 0.44) than non-Asians (mean = -0.07, sd = 0.36), but the size and direction of the differences varied considerably by domain, age, and gender.

Conclusion

When compared to norms, Asian patients showed no systematic biases. DIF results supported this finding. We conclude that Asian ethnicity does not impact interpretation of EORTC QLQ-C30 scores.
The factor structure and psychometric properties of the Chinese version of the Positive and Negative Suicide Ideation Inventory (PANSI-C) in a non-clinical sample of Chinese adolescents
Authors: Chen Wei , Yang Tao , Gao Rongfen , Zhang Guyin
Published: September 2021

Backgrounds

The Positive and Negative Suicide Ideation (PANSI) Inventory is a widely used self-report questionnaire which is designed to comprehensively evaluate the protective factors and negative risk factors associated with suicidal behaviors among adolescents. The present study aimed to evaluate the psychometric properties and measurement invariance of the Chinese version of the PANSI in a non-clinical sample of Chinese adolescents.

Methods

Participants (N = 1198) were Chinese middle school students aged 11–17 years (44.8% boys and 51.9% girls, 3.3% missing values) in Guizhou Province. All participants completed the Chinese version of the Positive and Negative Suicide Ideation Inventory (PANSI-C), the Rosenberg self-esteem scale (RSE), and the suicide probability scale (SPS). Cronbach’s alpha coefficients, confirmatory factor analysis, Pearson’s correlations, and multigroup confirmatory factor analysis tests were conducted thereafter.

Results

The results showed that the Cronbach’s alpha coefficients for the two subscales of the PANSI-positive suicide ideation and the PANSI-negative suicide ideation were .696 and .915, respectively. The confirmatory factor analysis supported the fit of the two-factor model as the best fitting model [Chi-square goodness of fit = 703.859, p < .001, degrees of freedom = 76, comparative fit index = .919, Tucker–Lewis index = .903, standardized root mean square residual = .047, root mean square error of approximation (90% CI) = .083 (.077, .089)]. Positive suicide ideation had negative correlations with the SPS and positive correlations with the RSE, whereas the negative suicide ideation had positive correlations with the SPS and negative correlations with the RSE. All correlations were statistically significant (p < .001), demonstrating the criterion validity of the PANSI-C. Moreover, the strict measurement invariance of the PANSI-C was supported across gender, single-parent and non-single-parent households groups, and the strong measurement invariance was supported across age.

Limitations

The feasibility of this study is limited to Chinese normal adolescents and lack of clinical samples.

Conclusion

Empirical support for the reliability and validity of the PANSI-C was found. The PANSI-C instrument is found to be useful in assessing positive and negative suicide ideation in Chinese normal adolescents.
Posttraumatic stress disorder and the risk of erectile dysfunction: a nationwide cohort study in Taiwan
Authors: Wang Sheng-Chiang , Chien Wu-Chien , Chung Chi-Hsiang , Tzeng Nian-Sheng , Liu Yia-Ping
Published: September 2021

Background

This study aimed to investigate the association between posttraumatic stress disorder and the risk of developing erectile dysfunction.

Methods

In this population-based retrospective cohort study, we used Taiwan’s National Health Insurance Research Database to analyze patients who were newly diagnosed with posttraumatic stress disorder (PTSD) between 2000 and 2013, with a 1:3 ratio by age and index year matched with patients in a non-PTSD comparison group, for the risk of erectile dysfunction.

Results

In total, 5 out of 1079 patients in the PTSD group developed erectile dysfunction, and 3 out of 3237 patients in the non-PTSD group (47.58 vs. 9.03 per 100,000 per person-year) developed erectile dysfunction. The Kaplan–Meier analysis showed that the PTSD cohort had a significantly higher risk of erectile dysfunction (log-rank,p < 0.001). The Cox regression analysis revealed that the study subjects were more likely to develop an injury (hazard ratio: 12.898, 95% confidence intervals = 2.453–67.811,p = 0.003) after adjusting for age, monthly income, urbanization level, geographic region, and comorbidities. Psychotropic medications used by the patients with PTSD were not associated with the risk of erectile dysfunction.

Conclusions

Patients who suffered from PTSD had a higher risk of developing erectile dysfunction.
A left lung with four lobes: a new discovery during the thoracotomy for recurrent primary spontaneous pneumothorax
Authors: Mehrabi Saadat , Tanideh Nader , Hosseinpour Reza , Irajie Cambyz , Yavari Barhaghtalabi Mohammad Javad
Published: September 2021

Background

The right and left lung anatomy are similar but asymmetrical. The right lung consists of three lobes, and the left lung consists of two lobes. Our study is unique because of discovering a very rare morphological feature of the left lung which has not been reported yet. By the way, we compared two different available chemical agents for pleurodesis (talc and bleomycin) according to side effects, complications, and pneumothorax recurrence.

Case presentation

We reported a case of bilateral primary spontaneous pneumothorax, who underwent talc slurry and bleomycin pleurodesis at right and left side retrospectively, and then complicate with left-sided recurrent spontaneous pneumothorax, so underwent open thoracotomy and was surprisingly and accidentally found to have 4 lobes and 3 fissures in left lung.

Conclusion

In our case report, there were one main oblique fissure and two accessory fissures which divided the lung into 4 separated lobes, and this discovery in human’s and other animals’ lung anatomy has not been previously reported. In our case study, the talc slurry was more effective in preventing spontaneous pneumothorax recurrence, but with more side effects than bleomycin. We could hypothesize that the morphological variation of the lung might affect spontaneous pneumothorax development and recurrence.
Chemical profiles and metabolite study of raw and processed Cistanche deserticola in rats by UPLC-Q-TOF-MSE
Authors: Li Zhe , Ryenchindorj Lkhaasuren , Liu Bonan , Shi Ji , Zhang Chao , Hua Yue , Liu Pengpeng , Shan Guoshun , Jia Tianzhu
Published: September 2021

Background

Chinese materia medica processing is a distinguished and unique pharmaceutical technique in Traditional Chinese Medicine (TCM) used for reducing side effects, and increasing or even changing therapeutic efficacy of the raw herbs.Changes in the essential components induced by an optimized processing procedure are primarily responsible for the increased efficacy of medicinal plants.The kidney-yang invigorating effect of rice wine-steamed Cistancha deserticola (C. deserticola) was stronger than raw C. deserticola (CD).

Methods

A comparison analysis was carried out using the UPLC-Q-TOF-MSE with the UNIFI informatics platform to determine the influence of processing. In vitro studies were performed for the characterization of constituents as well as metabolites in vivo. The chemical components were determined in CD and its processed products. The multivariate statistical analyses were conducted to evaluate variations between them while OPLS-DA was used for pairwise comparison.

Results

The results of this study revealed considerable variations in phenylethanoid glycosides (PhGs) and iridoids after processing. A total of 97 compounds were detected in the extracts of CD and its processed product. PhGs having 4'-O-caffeoyl group in the 8-O-β-d-glucopyranosyl part, like acteoside, cistanoside C, campneoside II, osmanthuside decreased after being processed, while PhGs with 6'-O-caffeoyl group in the 8-O-β-d-glucopyranosyl part, such as isoacetoside, isocistanoside C, isocampneoside I, isomartynoside increased, especially in the CD-NP group. The intensity of echinacoside and cistanoside B whose structure possess 6'-O-β-d-glucopyranosyl moiety also increased. In in vivo study, 10 prototype components and 44 metabolites were detected in rat plasma, feces, and urine. The obtained results revealed that processing leads to the considerable variation in the chemical constituents of CD and affected the disposition of the compounds in vivo, and phase II metabolic processes are the key cascades of each compound and most of the metabolites are associated with echinacoside or acteoside.

Conclusions

This is the first global comparison research of raw and processed CD. These findings add to our understanding of the impact of CD processing and give important data for future efficacy investigations.
Evaluation of the parents’ anxiety levels before and after the diagnosis of their child with a rare genetic disease: the necessity of psychological support
Authors: Kolemen Ayse B. , Akyuz Enes , Toprak Ali , Deveci Erdem , Yesil Gozde
Published: September 2021

Background

The diagnosis of the rare genetic diseases has great importance in treating multisystemic conditions, preventing potential complications, and estimating disease risk for family members. The duration of obtaining genetic test results is varies. The demand to learn the diagnosis of a possible untreatable illness involves a struggle between uncertainty and a lifetime chronic disease. The current uncertainty of their child's condition and the long wait for a diagnosis may increase the parents' anxiety level and cause difficulties in the continuation of diagnostic procedures in some families. This study aimed to investigate the prediagnosis and postdiagnosis anxiety levels of parents who have a child with a rare genetic disease.

Method

The parents in this study, mothers or fathers, admitted their children to the Bezmialem Vakıf University Medical Genetics Clinic due to a suspected rare genetic disease (n = 40). Researchers created “The Sociodemographic Questionnaire” and used it to analyze the parents' sociodemographic status. In addition, they used the State-Trait Anxiety Inventory (STAI) to determine the anxiety levels of the parents.

Results

The state anxiety levels of parents decreased significantly after learning the diagnosis. However, there was no statistically significant decrease observed in trait anxiety levels.

Conclusion

Data from this study revealed that informing parents about their child's disease and properly explaining to them the expected difficulties might help to reduce their anxiety levels. Psychological support for parents is necessary to reduce their long-term stress, thus increasing the patient's compliance with treatment.
Ackr3-Venus knock-in mouse lights up brain vasculature
Authors: Ehrlich Aliza T. , Semache Meriem , Couvineau Pierre , Wojcik Stefan , Kobayashi Hiroyuki , Thelen Marcus , Gross Florence , Hogue Mireille , Le Gouill Christian , Darcq Emmanuel , Bouvier Michel , Kieffer Brigitte L.
Published: September 2021

The atypical chemokine receptor 3, ACKR3, is a G protein-coupled receptor, which does not couple to G proteins but recruits βarrestins. At present, ACKR3 is considered a target for cancer and cardiovascular disorders, but less is known about the potential of ACKR3 as a target for brain disease. Further, mouse lines have been created to identify cells expressing the receptor, but there is no tool to visualize and study the receptor itself under physiological conditions. Here, we engineered a knock-in (KI) mouse expressing a functional ACKR3-Venus fusion protein to directly detect the receptor, particularly in the adult brain. In HEK-293 cells, native and fused receptors showed similar membrane expression, ligand induced trafficking and signaling profiles, indicating that the Venus fusion does not alter receptor signaling. We also found that ACKR3-Venus enables direct real-time monitoring of receptor trafficking using resonance energy transfer. In ACKR3-Venus knock-in mice, we found normal ACKR3 mRNA levels in the brain, suggesting intact gene transcription. We fully mapped receptor expression across 14 peripheral organs and 112 brain areas and found that ACKR3 is primarily localized to the vasculature in these tissues. In the periphery, receptor distribution aligns with previous reports. In the brain there is notable ACKR3 expression in endothelial vascular cells, hippocampal GABAergic interneurons and neuroblast neighboring cells. In conclusion, we have generated Ackr3-Venus knock-in mice with a traceable ACKR3 receptor, which will be a useful tool to the research community for interrogations about ACKR3 biology and related diseases.
Current status of research on exosomes in general, and for the diagnosis and treatment of kidney cancer in particular
Authors: Mao Weipu , Wang Keyi , Wu Zonglin , Xu Bin , Chen Ming
Published: September 2021

Kidney cancer is a common urological tumour. Owing to its high prevalence and mortality rate, it is the third most malignant tumour of the urinary system, followed by prostate and bladder cancers. It exerts a high degree of malignancy, and most of the distant metastasis occurs at an early stage; it is insensitive to chemoradiotherapy and easily develops drug resistance. The current treatment for kidney cancer mainly includes surgery, interventional embolization and targeted therapy; however, the treatment efficacy is poor. In recent years, the role of exosomes as mediators of intercellular communication and information exchange in the tumour microenvironment in tumour pathogenesis has attracted much attention. Exosomes are rich in bioactive substances such as nucleic acids, proteins and lipids and are involved in angiogenesis, immune regulation, drug resistance, formation of pre-metastatic niche, invasion and metastasis. This article reviews the ongoing research and applications of exosomes for the diagnosis and treatment of kidney cancer.
A new scoring system and clinical algorithm for the management of suspected foreign body aspiration in children: a retrospective cohort study
Authors: Fasseeh Nader A. , Elagamy Osama A. , Gaafar Alaa H. , Reyad Heba M. , Abougabal Mohamed S. , Heiba Doaa A. , Kantar Ahmad
Published: September 2021

Background

Cases of foreign body aspiration in children may be encountered in emergency departments. A suggestive history is important in diagnosing aspirated foreign body owing to the difficulty in making a diagnosis on the basis of an abnormal physical examination or chest radiography alone. The aim of this study was to examine the sensitivity and specificity of the presenting symptoms, physical examination, and radiologic findings as predictors of foreign body aspiration in children. In addition, a feasible simple algorithm with a scoring system was generated to indicate bronchoscopic investigation.

Methods

In a retrospective cohort, medical records of patients aged less than 16 years with suspected foreign body aspiration who underwent flexible or rigid bronchoscopy were included. Data including age, sex, symptoms, physical examination findings, radiological features, nature and location of the foreign body, and outcome of the bronchoscopy were collected, and multivariable binary logistic regression analysis was employed for prediction of foreign body aspiration.

Results

A total of 203 children were included, and the model showed excellent discrimination power for positive foreign body aspiration (area under the curve = 0.911) with an accuracy, sensitivity, and specificity of 86.2, 90.6, and 76.6%, respectively. The total weighted risk score at a cut-off > 2 showed a significant good power of discrimination (area under the curve = 0.879), with a sensitivity of 79.9% and specificity of 84.4%. Accordingly, a clinical algorithm was recommended.

Conclusions

The proposed scoring system and clinical algorithm might help in decision making with regard to the need and type of bronchoscopy in children presenting with potential foreign body aspiration. However, further prospective multicenter studies should be conducted to validate this scoring system.
Novel missense mutation of the TP63 gene in a newborn with Hay-Wells/Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome: clinical report and follow-up
Authors: Serra Gregorio , Antona Vincenzo , Giuffré Mario , Li Pomi Federica , Lo Scalzo Lucia , Piro Ettore , Schierz Ingrid Anne Mandy , Corsello Giovanni
Published: September 2021

Introduction

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare genetic syndrome with ectodermal dysplasia. About 100 patients have been reported to date. It is associated to a heterozygous mutation of the tumor protein p63 (TP63) gene, located on chromosome 3q28. Typical clinical manifestations include: filiform ankyloblepharon adnatum (congenital adherence of the eyelids), ectodermal abnormalities (sparse and frizzy hair, skin defects, nail alterations, dental changes and hypohidrosis), and cleft lip/palate. Diagnostic suspicion is based on clinical signs and confirmed by genetic testing.

Patient’s presentation

We hereby report on a female newborn with erythroderma, thin lamellar desquamations, extensive skin erosions, sparse and wiry hair, filiform ankyloblepharon adnatum, agenesis of the lachrymal puncta, cleft palate and nail dysplasia. Her phenotype was compatible with AEC syndrome. Then, based on the clinical suspicion, sequencing analysis of the TP63 gene was performed, and revealed a de novo novel missense mutation. Eyelids adherence and cleft palate underwent surgical correction, while skin erosions were treated with topical antibiotics/antifungals and emollient/re-epithelizing creams. A surgical reconstruction is presently planned for the agenesis of the lachrymal puncta. The infant currently is 17 months of age and is included in a multidisciplinary follow-up. At present shows growth impairment and mild developmental delay, and typical signs of ectodermal dysplasia with small areas of dermatitis lesions on the scalp, without further abnormalities.

Conclusions

Our report underlines the relevance of an early and careful clinical evaluation in neonates with ankyloblefaron, facial dysmorphism, and signs of ectodermal dysplasia. In these cases, the suspicion of AEC syndrome must be promptly raised, and sequencing analysis of TP63 early performed as well. An individualized, multidisciplinary and long-term follow-up should be guaranteed to affected subjects and their families, also to identify associated morbidities and prevent possible serious complications and adverse outcomes.
Activity of the mouse Notch ligand DLL1 is sensitive to C-terminal tagging in vivo
Authors: Schuster-Gossler Karin , Boldt Karsten , Bornhorst Dorothee , Delany-Heiken Patricia , Ueffing Marius , Gossler Achim
Published: September 2021

Objective

The mammalian Notch ligand DLL1 has essential functions during development. To visualise DLL1 in tissues, for sorting and enrichment of DLL1-expressing cells, and to efficiently purify DLL1 protein complexes we tagged DLL1 in mice with AcGFPHA or Strep/FLAG.

Results

We generated constructs to express DLL1 that carried C-terminal in-frame an AcGFPHA tag flanked by loxP sites followed by a Strep/FLAG (SF) tag out of frame. Cre-mediated recombination replaced AcGFP-HA by SF. The AcGFPHAstopSF cassette was added to DLL1 for tests in cultured cells and introduced into endogenous DLL1 in mice by homologous recombination. Tagged DLL1 protein was detected by antibodies against GFP and HA or Flag, respectively, both in CHO cells and embryo lysates. In CHO cells the AcGFP fluorophore fused to DLL1 was functional. In vivo AcGFP expression was below the level of detection by direct fluorescence. However, the SF tag allowed us to specifically purify DLL1 complexes from embryo lysates. Homozygous mice expressing AcGFPHA or SF-tagged DLL1 revealed a vertebral column phenotype reminiscent of disturbances in AP polarity during somitogenesis, a process most sensitive to reduced DLL1 function. Thus, even small C-terminal tags can impinge on sensitive developmental processes requiring DLL1 activity.
Fabrication of alginate-based hydrogel cross-linked via horseradish peroxidase for articular cartilage engineering
Authors: Saghati Sepideh , Khoshfetrat Ali Baradar , Tayefi Nasrabadi Hamid , Roshangar Leila , Rahbarghazi Reza
Published: September 2021

Objective

We aimed to detect the effect of a couple of parameters including Alg, H2O2, and HRP concentrations on the gelation time of Alg-based hydrogels using an enzymatic cross-linked procedure.

Results

NMR, UV–Vis, and ATR-FTIR analyses confirmed the conjugation of Ph to the Alg backbone. Data showed gelation time was delayed with the increase and reduction of H2O2 and HRP, respectively. We noted that hydrogel consisted of 1.2% (w/v) Alg, 5 U HRP, and 100 mM H2O2 yielded an appropriate gelation time with appropriate mechanical properties. The addition of 0.5% (v/v) Col developed hydrogel increased the gelation time. The data showed that Alg, HRP, and H2O2 with the ratio of 1:0.54:0.54 had proper physicochemical features for cartilage engineering.
Investigating the DNA methylation profile of e-cigarette use
Authors: Richmond Rebecca C. , Sillero-Rejon Carlos , Khouja Jasmine N. , Prince Claire , Board Alexander , Sharp Gemma , Suderman Matthew , Relton Caroline L. , Munafò Marcus , Gage Suzanne H.
Published: September 2021

Background

Little evidence exists on the health effects of e-cigarette use. DNA methylation may serve as a biomarker for exposure and could be predictive of future health risk. We aimed to investigate the DNA methylation profile of e-cigarette use.

Results

Among 117 smokers, 117 non-smokers and 116 non-smoking vapers, we evaluated associations between e-cigarette use and epigenome-wide methylation from saliva. DNA methylation at 7 cytosine-phosphate-guanine sites (CpGs) was associated with e-cigarette use atp < 1 × 10–5and none atp < 5.91 × 10–8. 13 CpGs were associated with smoking atp < 1 × 10–5and one atp < 5.91 × 10–8. CpGs associated with e-cigarette use were largely distinct from those associated with smoking. There was strong enrichment of known smoking-related CpGs in the smokers but not the vapers. We also tested associations between e-cigarette use and methylation scores known to predict smoking and biological ageing. Methylation scores for smoking and biological ageing were similar between vapers and non-smokers. Higher levels of all smoking scores and a biological ageing score (GrimAge) were observed in smokers. A methylation score for e-cigarette use showed poor prediction internally (AUC 0.55, 0.41–0.69) and externally (AUC 0.57, 0.36–0.74) compared with a smoking score (AUCs 0.80) and was less able to discriminate lung squamous cell carcinoma from adjacent normal tissue (AUC 0.64, 0.52–0.76 versus AUC 0.73, 0.61–0.85).

Conclusions

The DNA methylation profile for e-cigarette use is largely distinct from that of cigarette smoking, did not replicate in independent samples, and was unable to discriminate lung cancer from normal tissue. The extent to which methylation related to long-term e-cigarette use translates into chronic effects requires further investigation.
Machine learning methods for predicting progression from mild cognitive impairment to Alzheimer’s disease dementia: a systematic review
Authors: Grueso Sergio , Viejo-Sobera Raquel
Published: September 2021

Background

An increase in lifespan in our society is a double-edged sword that entails a growing number of patients with neurocognitive disorders, Alzheimer’s disease being the most prevalent. Advances in medical imaging and computational power enable new methods for the early detection of neurocognitive disorders with the goal of preventing or reducing cognitive decline. Computer-aided image analysis and early detection of changes in cognition is a promising approach for patients with mild cognitive impairment, sometimes a prodromal stage of Alzheimer’s disease dementia.

Methods

We conducted a systematic review following PRISMA guidelines of studies where machine learning was applied to neuroimaging data in order to predict whether patients with mild cognitive impairment might develop Alzheimer’s disease dementia or remain stable. After removing duplicates, we screened 452 studies and selected 116 for qualitative analysis.

Results

Most studies used magnetic resonance image (MRI) and positron emission tomography (PET) data but also magnetoencephalography. The datasets were mainly extracted from the Alzheimer’s disease neuroimaging initiative (ADNI) database with some exceptions. Regarding the algorithms used, the most common was support vector machine with a mean accuracy of 75.4%, but convolutional neural networks achieved a higher mean accuracy of 78.5%. Studies combining MRI and PET achieved overall better classification accuracy than studies that only used one neuroimaging technique. In general, the more complex models such as those based on deep learning, combined with multimodal and multidimensional data (neuroimaging, clinical, cognitive, genetic, and behavioral) achieved the best performance.

Conclusions

Although the performance of the different methods still has room for improvement, the results are promising and this methodology has a great potential as a support tool for clinicians and healthcare professionals.
Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis
Authors: Ning Hongjuan , Chen Haixu , Deng Jingyu , Xiao Chun , Xu Moyan , Shan Lina , Yang Chao , Zhang Zheng
Published: September 2021

Background

Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secrete more exosomes, but little was known on MI repair.

Methods

Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization.

Results

Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs-Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF‐κB signaling pathway and upregulated Nrf2/HO-1 Axis.

Conclusions

FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI.