bluuebunny/crossref_metadata_2025 huggingface dataset:
Public Opinions About Child Maltreatment in South Carolina: Salience, Relevance, Prevention, and Support for Government Intervention
Authors: Srivastav Aditi , Nelson Katherine , Strompolis Melissa , Purtle Jonathan
Published: June 2021

Substantial evidence demonstrates that child maltreatment is preventable through approaches that address the socio-environmental contexts that shape attitudes and behaviors. Understanding opinions about child maltreatment can inform efforts to influence policy and practice changes that promote child health and well-being. This study examined public opinions about child maltreatment in South Carolina. A telephone survey was conducted in Fall 2019 with a random sample of adults ( N = 1,145) in the state. Respondents rated the extent to which they agreed that child maltreatment is an important issue (salience), whether it is a problem in their community (relevance), whether it is preventable (prevention orientation), whether child maltreatment prevention is a good use of their tax dollars, and whether child maltreatment can be prevented through government intervention. Stronger issue salience was significantly associated with stronger beliefs about government intervention to prevent child maltreatment after adjustment for demographics ( B = 0.69, p < .0001). Stronger issue relevance ( B = 0.05, p = .08) and stronger prevention orientation ( B = 0.19, p < .001) were also significantly associated with stronger beliefs about government intervention to prevent child maltreatment after adjustment for demographics. Results indicate that changing public opinions about child maltreatment—specifically around issue salience, relevance, and prevention orientation—could have implications for communications interventions that seek to generate support for government intervention to prevent child maltreatment.
Utilization of Platelet-Rich Plasma (PRP) to Reconstruct Bilateral Mandibular Defects
Authors: Haas Justin , Teshima Tara Lynn
Published: June 2021

Background: Platelet-rich plasma (PRP) plus bone substitute matrix used to repair defects in the viscerocranium has been demonstrated to be equally as effective at regenerating bone as autografts. The creation of fewer surgical sites, reduced operative and recovery time, and infection prevention are all potential benefits of this novel approach, especially for patients with conditions that complicate surgical management and recovery. Case presentation: A 33-year-old male with schizophrenia presented with trauma-induced bilateral mandibular fractures. Premorbid mental health factors and a complicated clinical trajectory precluded traditional management using bone autografts to repair mandibular defects and restore occlusive alignment. Instead, a composite matrix consisting of cadaver-derived bone chips and PRP was used to span 1 and 1.5 cm mandibular gaps. No complications were identified and occlusion with adequate alignment and function was achieved. Conclusion: We report the first patient to undergo surgical repair for multiple trauma-induced mandibular bone defects using a matrix made only of bone substitute and PRP.
A ground-motion prediction model for small-to-moderate induced earthquakes for Central and Eastern United States
Authors: Farajpour Zoya , Pezeshk Shahram
Published: June 2021

This study presents a new ground motion model (GMM) for small-to-moderate potentially induced earthquakes for Central and Eastern United States (CEUS). We used a hybrid empirical model as the base model, which was developed and calibrated for tectonic events in Central and Eastern North America (CENA) as part of the Next-generation Attenuation-East (NGA-East) project. We calibrated the base model using a comprehensive database of potentially induced ground motions with smaller magnitudes and shallower depths than tectonic earthquakes, excluding all earthquake events and stations within the Gulf Coast region. We determined the model functional form coefficients using a mixed-effect regression procedure. The proposed GMM is derived for the peak ground acceleration and response-spectral ordinates at periods ranging from 0.01 to 10.0s, moment magnitudes ranging from 3.0 to 5.8, and hypocentral distances up to 200km. The performance of the proposed GMM is evaluated through a set of comprehensive residual analyses. Furthermore, we compared the proposed GMM with recently published GMMs with the observed data for CEUS. The proposed GMM could apply in long-term and short-term US Geological Survey National Seismic Hazard Maps and for the hazard evaluation of induced seismicity.
Patient characteristics, biomarkers and exacerbation risk in severe, uncontrolled asthma
Authors: Kraft Monica , Brusselle Guy , FitzGerald J. Mark , Pavord Ian D. , Keith Matthew , Fagerås Malin , Garcia Gil Esther , Hirsch Ian , Goldman Mitchell , Colice Gene
Published: June 2021

Background

Greater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma.

Methods

Data were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualised asthma exacerbation rates (AAERs) for patients randomised to placebo were assessed by baseline clinical characteristics, and by biomarker concentrations at baseline and over the study duration.

Results

The AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race and Asian or Western European region. AAER increased with baseline blood eosinophil counts and exhaled nitric oxide fraction (FENO) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL−1andFENO≥50 ppb. No relationship was observed between baseline serum IgE concentration and AAER. Combining type 2 inflammation criteria for eosinophils andFENOhad greater prognostic value than either biomarker alone. Persistent eosinophil andFENOelevations throughout the study period were associated with greater AAER.

Conclusions

Exacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts andFENOconcentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.
Deep Spatiotemporal Convolutional-Neural-Network-Based Remaining Useful Life Estimation of Bearings
Authors: Wang Xu , Wang Tianyang , Ming Anbo , Han Qinkai , Chu Fulei , Zhang Wei , Li Aihua
Published: June 2021

The remaining useful life (RUL) estimation of bearings is critical for ensuring the reliability of mechanical systems. Owing to the rapid development of deep learning methods, a multitude of data-driven RUL estimation approaches have been proposed recently. However, the following problems remain in existing methods: 1) Most network models use raw data or statistical features as input, which renders it difficult to extract complex fault-related information hidden in signals; 2) for current observations, the dependence between current states is emphasized, but their complex dependence on previous states is often disregarded; 3) the output of neural networks is directly used as the estimated RUL in most studies, resulting in extremely volatile prediction results that lack robustness. Hence, a novel prognostics approach is proposed based on a time–frequency representation (TFR) subsequence, three-dimensional convolutional neural network (3DCNN), and Gaussian process regression (GPR). The approach primarily comprises two aspects: construction of a health indicator (HI) using the TFR-subsequence–3DCNN model, and RUL estimation based on the GPR model. The raw signals of the bearings are converted into TFR-subsequences by continuous wavelet transform and a dislocated overlapping strategy. Subsequently, the 3DCNN is applied to extract the hidden spatiotemporal features from the TFR-subsequences and construct HIs. Finally, the RUL of the bearings is estimated using the GPR model, which can also define the probability distribution of the potential function and prediction confidence. Experiments on the PRONOSTIA platform demonstrate the superiority of the proposed TFR-subsequence–3DCNN–GPR approach. The use of degradation-related spatiotemporal features in signals is proposed herein to achieve a highly accurate bearing RUL prediction with uncertainty quantification.
PPalign: optimal alignment of Potts models representing proteins with direct coupling information
Authors: Talibart Hugo , Coste François
Published: June 2021

Background

To assign structural and functional annotations to the ever increasing amount of sequenced proteins, the main approach relies on sequence-based homology search methods, e.g. BLAST or the current state-of-the-art methods based on profile Hidden Markov Models, which rely on significant alignments of query sequences to annotated proteins or protein families. While powerful, these approaches do not take coevolution between residues into account. Taking advantage of recent advances in the field of contact prediction, we propose here to represent proteins by Potts models, which model direct couplings between positions in addition to positional composition, and to compare proteins by aligning these models. Due to non-local dependencies, the problem of aligning Potts models is hard and remains the main computational bottleneck for their use.

Methods

We introduce here an Integer Linear Programming formulation of the problem and PPalign, a program based on this formulation, to compute the optimal pairwise alignment of Potts models representing proteins in tractable time. The approach is assessed with respect to a non-redundant set of reference pairwise sequence alignments from SISYPHUS benchmark which have lowest sequence identity (between $$3\%$$

3
%

and $$20\%$$

20
%

) and enable to build reliable Potts models for each sequence to be aligned. This experimentation confirms that Potts models can be aligned in reasonable time ($$1'37''$$

1
′

37

′
′

in average on these alignments). The contribution of couplings is evaluated in comparison with HHalign and independent-site PPalign. Although Potts models were not fully optimized for alignment purposes and simple gap scores were used, PPalign yields a better mean $$F_1$$

F
1

score and finds significantly better alignments than HHalign and PPalign without couplings in some cases.

Conclusions

These results show that pairwise couplings from protein Potts models can be used to improve the alignment of remotely related protein sequences in tractable time. Our experimentation suggests yet that new research on the inference of Potts models is now needed to make them more comparable and suitable for homology search. We think that PPalign’s guaranteed optimality will be a powerful asset to perform unbiased investigations in this direction.
Mapping methylation quantitative trait loci in cardiac tissues nominates risk loci and biological pathways in congenital heart disease
Authors: Li Ming , Lyu Chen , Huang Manyan , Do Catherine , Tycko Benjamin , Lupo Philip J. , MacLeod Stewart L. , Randolph Christopher E. , Liu Nianjun , Witte John S. , Hobbs Charlotte A.
Published: June 2021

Background

Most congenital heart defects (CHDs) result from complex interactions among genetic susceptibilities, epigenetic modifications, and maternal environmental exposures. Characterizing the complex relationship between genetic, epigenetic, and transcriptomic variation will enhance our understanding of pathogenesis in this important type of congenital disorder. We investigated cis-acting effects of genetic single nucleotide polymorphisms (SNPs) on local DNA methylation patterns within 83 cardiac tissue samples and prioritized their contributions to CHD risk by leveraging results of CHD genome-wide association studies (GWAS) and their effects on cardiac gene expression.

Results

We identified 13,901 potential methylation quantitative trait loci (mQTLs) with a false discovery threshold of 5%. Further co-localization analyses and Mendelian randomization indicated that genetic variants near the HLA-DRB6 gene on chromosome 6 may contribute to CHD risk by regulating the methylation status of nearby CpG sites. Additional SNPs in genomic regions on chromosome 10 (TNKS2-AS1 gene) and chromosome 14 (LINC01629 gene) may simultaneously influence epigenetic and transcriptomic variations within cardiac tissues.

Conclusions

Our results support the hypothesis that genetic variants may influence the risk of CHDs through regulating the changes of DNA methylation and gene expression. Our results can serve as an important source of information that can be integrated with other genetic studies of heart diseases, especially CHDs.
Internal validation and comparison of the prognostic performance of models based on six emergency scoring systems to predict in-hospital mortality in the emergency department
Authors: Rahmatinejad Zahra , Tohidinezhad Fariba , Rahmatinejad Fatemeh , Eslami Saeid , Pourmand Ali , Abu-Hanna Ameen , Reihani Hamidreza
Published: June 2021

Background

Medical scoring systems are potentially useful to make optimal use of available resources. A variety of models have been developed for illness measurement and stratification of patients in Emergency Departments (EDs). This study was aimed to compare the predictive performance of the following six scoring systems: Simple Clinical Score (SCS), Worthing physiological Score (WPS), Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS), Modified Early Warning Score (MEWS), and Routine Laboratory Data (RLD) to predict in-hospital mortality.

Methods

A prospective single-center observational study was conducted from March 2016 to March 2017 in Edalatian ED in Emam Reza Hospital, located in the northeast of Iran. All variables needed to calculate the models were recorded at the time of admission and logistic regression was used to develop the models’ prediction probabilities. The Area Under the Curve for Receiver Operating Characteristic (AUC-ROC) and Precision-Recall curves (AUC-PR), Brier Score (BS), and calibration plots were used to assess the models’ performance. Internal validation was obtained by 1000 bootstrap samples. Pairwise comparison of AUC-ROC was based on the DeLong test.

Results

A total of 2205 patients participated in this study with a mean age of 61.8 ± 18.5 years. About 19% of the patients died in the hospital. Approximately 53% of the participants were male. The discrimination ability of SCS, WPS, RAPS, REMS, MEWS, and RLD methods were 0.714, 0.727, 0.661, 0.678, 0.698, and 0.656, respectively. Additionally, the AUC-PR of SCS, WPS, RAPS, REMS, EWS, and RLD were 0.39, 0.42, 0.35, 0.34, 0.36, and 0.33 respectively. Moreover, BS was 0.1459 for SCS, 0.1713 for WPS, 0.0908 for RAPS, 0.1044 for REMS, 0.1158 for MEWS, and 0.073 for RLD. Results of pairwise comparison which was performed for all models revealed that there was no significant difference between the SCS and WPS. The calibration plots demonstrated a relatively good concordance between the actual and predicted probability of non-survival for the SCS and WPS models.

Conclusion

Both SCS and WPS demonstrated fair discrimination and good calibration, which were superior to the other models. Further recalibration is however still required to improve the predictive performance of all available models and their use in clinical practice is still unwarranted.
Subjective and objective health predicting mortality and institutionalization: an 18-year population-based follow-up study among community-dwelling Finnish older adults
Authors: Viljanen Anna , Salminen Marika , Irjala Kerttu , Heikkilä Elisa , Isoaho Raimo , Kivelä Sirkka-Liisa , Korhonen Päivi , Vahlberg Tero , Viitanen Matti , Wuorela Maarit , Löppönen Minna , Viikari Laura
Published: June 2021

Background

Objective health measures, such as registered illnesses or frailty, predict mortality and institutionalization in older adults. Also, self-reported assessment of health by simple self-rated health (SRH) has been shown to predict mortality and institutionalization. The aim of this study was to assess the association of objective and subjective health with mortality and institutionalization in Finnish community-dwelling older adults.

Methods

In this prospective study with 10- and 18-year follow-ups, objective health was measured by registered illnesses and subjective health was evaluated by simple SRH, self-reported walking ability (400 m) and self-reported satisfaction in life. The participants were categorized into four groups according to their objective and subjective health: 1. subjectively and objectively healthy, 2. subjectively healthy and objectively unhealthy, 3. subjectively unhealthy and objectively healthy and 4. subjectively and objectively unhealthy. Cox regression model was used in the analyses. Death was used as a competing factor in the institutionalization analyses.

Results

The mean age of the participants (n = 1259) was 73.5 years (range 64.0–100.0). During the 10- and 18-year follow-ups, 466 (37%) and 877 (70%) died, respectively. In the institutionalization analyses (n = 1106), 162 (15%) and 328 (30%) participants were institutionalized during the 10- and 18-year follow-ups, respectively. In both follow-ups, being subjectively and objectively unhealthy, compared to being subjectively and objectively healthy, was significantly associated with a higher risk of institutionalization in unadjusted models and with death both in unadjusted and adjusted models.

Conclusions

The categorization of objective and subjective health into four health groups was good at predicting the risk of death during 10- and 18-year follow-ups, and seemed to also predict the risk of institutionalization in the unadjusted models during both follow-ups. Poor subjective health had an additive effect on poor objective health in predicting mortality and could therefore be used as part of an older individual’s health evaluation when screening for future adverse outcomes.
Topical estrogen, testosterone, and vaginal dilator in the prevention of vaginal stenosis after radiotherapy in women with cervical cancer: a randomized clinical trial
Authors: Martins Jumara , Vaz Ana Francisca , Grion Regina Celia , Costa-Paiva Lúcia , Baccaro Luiz Francisco
Published: June 2021

Background

We aimed to evaluate the effects of different therapeutic options to prevent the evolution of vaginal stenosis after pelvic radiotherapy in women with cervical cancer.

Methods

open-label randomized clinical trial of 195 women, stage I-IIIB, aged 18–75 years, using topical estrogen (66), topical testosterone (34), water-based intimate lubricant gel (66), and vaginal dilators (29) to assess the incidence and severity of vaginal stenosis after radiotherapy at UNICAMP-Brazil, from January/2013 to May/2018. The main outcome measure was vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE) scale and percental changes in vaginal volume. The women were evaluated at four different times: shortly after the end of radiotherapy, and four, eight, and 12 months after the beginning of the intervention. Statistical analysis was carried out using Symmetry test, Kruskal-Wallis test and multiple regression.

Results

the mean age of women was 46.78 (±13.01) years, 61,03% were premenopausal and 73,84% had stage IIB-IIIB tumors. The mean reduction in vaginal volume in the total group was 25.47%, with similar worsening in the four treatment groups with no statistical difference throughout the intervention period. There was worsening of vaginal stenosis evaluated by CTCAE scale after 1 year in all groups (p < 0.01), except for the users of vaginal dilator (p = 0.37).

Conclusions

there was a reduction in vaginal volume in all treatment groups analyzed, with no significant difference between them. However, women who used vaginal dilators had a lower frequency and severity of vaginal stenosis assessed by the CTCAE scale after one year of treatment.

Trial registration

Brazilian Registry of Clinical Trials, RBR-23w5fv. Registered 10 January 2017 - Retrospectively registered.
Identification of prognostic markers for hepatocellular carcinoma based on the epithelial-mesenchymal transition-related gene BIRC5
Authors: Xu Rongzhong , Lin Liubing , Zhang Bo , Wang Jian , Zhao Fanchen , Liu Xiaolin , Li Yiping , Li Yan
Published: June 2021

Background

The baculoviral IAP repeat containing 5 (BIRC5) related to epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of hepatocellular carcinoma (HCC). However, it remains unclear whether BIRC5-related genes can be used as prognostic markers of HCC.

Methods

Kaplan-Meier (K-M) survival curve was used to assess the Overall Survival (OS) of high- and low-expression group divided by the median of BIRC5 expression. The differentially expressed genes (DEGs) between the two groups were screened using the limma package, and performed the functional enrichment analysis by the clusterProfiler package. WGCNA was used to analyze the relationship of the module and the clinical traits. The risk signature was constructed by univariate and multivariate Cox regression analyses and the enrichment analysis of genes in the risk signature was performed by the Intelligent pathway analysis (IPA). The immunophenoscore (IPS) and the tumor immune dysfunction and exclusion (TIDE) were used to estimate the clinical significance of the risk groups.

Results

BIRC5 was high-expressed in HCC samples and associated with a poor prognosis (p-value < 0.0001). WGCNA screened 180 module genes which were overlapped with the 241 DEGs, ultimately getting 33 candidate genes. After the Cox regression analyses, CENPA, CDCA8, EZH2, KIF20A, KPNA2, CCNB1, KIF18B and MCM4 were preserved and used to construct risk signature, followed by calculating the risk score. The patients in high-risk groups stratified by median of the risk score were associated with a poor prognosis. The risk score had high accuracy [the area under the curve (AUC) > 0.72] and was closely associated with clinicopathological characteristics of HCC patients. IPA suggested that the 8 genes were enriched in Cancer and Immunological disease related pathways. IPS and TIDE score indicated that the genes in low-risk group could cause an immune response, and patients in the low-risk group may be more sensitive to the immune checkpoint blockade (ICB) therapy.

Conclusion

The risk score constructed by the 8 genes could not only predict the clinical outcome but also distinguish the cohort of ICB therapy in HCC, which exerted a vital value in treatment and prognosis of HCC.
High-level psychotropic polypharmacy: a retrospective comparison of children in foster care to their peers on Medicaid
Authors: Davis Deborah Winders , Lohr W. David , Feygin Yana , Creel Liza , Jawad Kahir , Jones V. Faye , Williams P. Gail , Le Jennifer , Trace Marie , Pasquenza Natalie
Published: June 2021

Background

The use of antipsychotic medication and psychotropic polypharmacy has increased in the United States over the last two decades especially for children from low-income families and those in foster care. Although attention has been paid to providing greater insight, prescribing patterns remain concerning since there is a lack of evidence related to safety and efficacy. High-level psychotropic polypharmacy has not been described. We aim to compare the use of HLPP for children receiving Medicaid services and those in foster care and identify factors associated with the duration of use of high-level psychotropic polypharmacy. Additionally, we will examine the frequency of laboratory metabolic screening and emergency department, inpatient, and outpatient visits.

Methods

A cross-sectional, secondary analysis of statewide data describes trends in high-level psychotropic polypharmacy from 2012 to 2017 and the prevalence and predictors of high-level psychotropic polypharmacy duration and resource use in 2017 for all children on Medicaid and those in foster care. High-level psychotropic polypharmacy included concurrent use, at least four classes of medications including an antipsychotic, and at least 30 days duration.

Results

High-level psychotropic polypharmacy increased from 2012 to 2014 for both groups but stabilized in 2015–2016. Children in foster care showed a slight increase compared to their peers in 2017. There was no association between duration and demographic characteristics or foster care status. Diagnoses predicted duration. Neither group received metabolic monitoring at an acceptable rate.

Conclusions

Concerning patterns of high-level psychotropic polypharmacy and metabolic monitoring were identified. Cautious use of high-level psychotropic polypharmacy and greater oversight to ensure that these children are receiving comprehensive services like behavioral health, primary care, and primary prevention.
Guidelines on analgosedation, monitoring, and recovery time for flexible bronchoscopy: a systematic review
Authors: Strohleit Daniel , Galetin Thomas , Kosse Nils , Lopez-Pastorini Alberto , Stoelben Erich
Published: June 2021

Background

Patients undergoing bronchoscopy in spontaneous breathing are prone to hypoxaemia and hypercapnia. Sedation, airway obstruction, and lung diseases impair respiration and gas exchange. The restitution of normal respiration takes place in the recovery room. Nonetheless, there is no evidence on the necessary observation time. We systematically reviewed current guidelines on bronchoscopy regarding sedation, monitoring and recovery.

Methods

This review was registered at the PROSPERO database (CRD42020197476). MEDLINE and awmf.org were double-searched for official guidelines, recommendation or consensus statements on bronchoscopy from 2010 to 2020. The PICO-process focussed on adults (Patients), bronchoscopy with maintained spontaneous breathing (Interventions), and recommendations regarding the intra- and postprocedural monitoring and sedation (O). The guideline quality was graded. A catalogue of 54 questions was answered. Strength of recommendation and evidence levels were recorded for each recommendation.

Results

Six guidelines on general bronchoscopy and three expert statements on special bronchoscopic procedures were identified. Four guidelines were evidence-based. Most guidelines recommend sedation to improve the patient’s tolerance. Midazolam combined with an opioid is preferred. The standard monitoring consists of non-invasive blood pressure, and pulse oximetry, furthermore electrocardiogram in cardiac patients. Only one guideline discusses hypercapnia and capnometry, but without consensus. Two guidelines discuss a recovery time of two hours, but a recommendation was not given because of lack of evidence.

Conclusion

Evidence for most issues is low to moderate. Lung-diseased patients are not represented by current guidelines. Capnometry and recovery time lack evidence. More primary research in these fields is needed so that future guidelines may address these issues, too.
Polysaccharides from Ganoderma Sinense - rice bran fermentation products and their anti-tumor activities on non-small-cell lung cancer
Authors: Han Wei , Chen Hongjuan , Zhou Lin , Zou Haijie , Luo Xiaohong , Sun Bo , Zhuang Xuhui
Published: June 2021

Background

Non-small-cell lung cancer (NSCLC) accounts more than 80% of the lung cancer cases. Polysaccharides in rice bran and its fermentation products have been proven to suppress many cancers. However, the report on inhibiting NSCLC is few. In this paper, the polysaccharides with suppression activity to H1299 NSCLC in the fermentation products of full-fat rice bran and defatted rice bran were studied in vitro and in vivo.

Method

Polysaccharides (GSRBPs) were extracted from Ganoderma sinense – full-fat rice bran (GS-FRB) and Ganoderma sinense – defatted rice bran (GS-DRB) fermentation products. The structure information of the GSRBPs was studied using HPLC analysis. The anti-tumor activities on H1299 NSCLC of GSRBPs in vitro study was performed using MTT method. The in vivo studies use BALB/c-nu nude mice as H1299 NSCLC bearing mice.

Result

All the polysaccharides contained two fractions, GSFPS-1 and GSFPS-2. The molecular weight and the ratio of GSFPS-1 and GSFPS-2 were different in GS-FRB and GS-DRB. At the earlier state of fermentation, all polysaccharides were composed of D-glu, D-man, D-xyl and L-ara with certain molar ratios. But at the latter stage, polysaccharides in GS-FRB were composed of D-glu, D-man, D-xyl, L-ara and D-fru, while these in GS-DRB only composed of D-glu and D-man. In the in vitro study, the IC50 of RBS and GSRBPs was as GS-DRB-11 (40.62 μg/mL), GS-FRB-9 (43.82 μg/mL), GS-DRB-7 (48.08 μg/mL), RBS (49.56 μg/mL), GS-DRB-9 (49.91 μg/mL), GS-DRB-13 (51.89 μg/mL), GS-FRB-11 (53.75 μg/mL), GS-FRB-7 (56.84 μg/mL), GS-DRB-13 (60.63 μg/mL) from small to large. In the in vivo study, the H1299 NSCLC inhibition rate (InRa) of RBS and GSRBPs were GS-DRB-11 (86.81%) > GS-DRB-9 (86.01%) > GS-FRB-9 (84.88%) > GS-DRB-7 (82.21%) > GS-DRB-13 (78.04%) > RBS (76.06%) > GS-FRB-13 (65.44%) > GS-FRB-11 (64.70%) > GS-FRB-7 (27.87%). The GSFPS-2 area percent was negatively correlated to the IC50 and was positively correlated to the InRa. This means the GSFPS-2 had much higher anti-tumor activity than GSFPS-1.

Conclusion

GSFPS-2 had higher anti-tumor activities, and the lipid in the rice bran has a decisive effect on the structures of polysaccharides produced by fermentation. Therefore, GSRBPs could be considered as potential novel agents to suppress H1299 non-small-cell lung cancer.
Mechanisms of impact and experiences of a person-centred transition programme for adolescents with CHD: the Stepstones project
Authors: Saarijärvi Markus , Wallin Lars , Moons Philip , Gyllensten Hanna , Bratt Ewa-Lena
Published: June 2021

Background

During the past decade there has been some evaluation of transition programmes for adolescents with chronic conditions. However, this has rarely involved process evaluations focusing on mechanisms leading to outcomes, thus hampering implementation of these complex interventions. Our aim was to (I) describe adolescents’ and parents’ experiences of participating in a person-centred transition programme aiming to empower them in transition to adulthood and (II) explore the mechanisms of impact.

Methods

A qualitative process evaluation was performed, embedded in a randomized controlled trial evaluating the effectiveness of a transition programme for adolescents with congenital heart disease in Sweden. A purposive sample of 14 adolescents and 12 parents randomized to the intervention group were interviewed after participation in the programme. Data were analysed deductively and inductively in NVivo v12.

Results

Experiences of participation in the transition programme were generally positive. Meeting a transition coordinator trained in person-centred care and adolescent health and embarking on an educational process based on the adolescents’ prerequisites in combination with peer support were considered key change mechanisms. However, support to parents were not sufficient for some participants, resulting in ambivalence about changing roles and the unmet needs of parents who required additional support.

Conclusions

Participants experienced increased empowerment in several dimensions of this construct, thus demonstrating that the transition programme was largely implemented as intended and the evidence-based behaviour-change techniques used proved effective in reaching the outcome. These findings can inform future implementation of transition programmes and illuminate challenges associated with delivering a complex intervention for adolescents with chronic conditions.
A meta-analysis of the efficacy and safety of adjuvant sorafenib for hepatocellular carcinoma after resection
Authors: Huang Shenglan , Li Dan , Zhuang LingLing , Sun Liying , Wu Jianbing
Published: June 2021

Background

Sorafenib was reported as a useful adjuvant treatment in patients with hepatocellular carcinoma who underwent surgical resection. However, its therapeutic value remains controversial. This meta-analysis examined the available data regarding the efficacy and safety of sorafenib in patients with hepatocellular carcinoma after radical surgery.

Methods

The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in advance with PROSPERO (CRD42021233868). We searched PubMed, Embase, Cochrane Library, and Web of Science to identify eligible studies. Overall survival, recurrence-free survival, and recurrence rates were analyzed, and adverse events were reviewed. Hazard ratios or pooled risk ratios with 95% CIs were collected and analyzed using STATA version 12.0 in a fixed-effects or random-effects meta-analysis model.

Results

In total, 2655 patients from 13 studies were ultimately included in this meta-analysis. The combined results illustrated that sorafenib was associated with better overall survival than the control (hazard ratio = 0.71, 95% CI = 0.59–0.86; P < 0.001). Similarly, the drug also improved recurrence-free survival (hazard ratio = 0.68, 95% CI = 0.54–0.86, P = 0.001). Combined data revealed that patients treated with sorafenib after resection had a lower recurrence rate (pooled risk ratio = 0.78, 95% CI = 0.68–0.90, P < 0.001). The primary adverse events were hand-foot skin reaction, fatigue, and diarrhea of mild-to-moderate severity, whereas grade 4 adverse events were rare (< 1%).

Conclusions

This meta-analysis demonstrated that adjuvant sorafenib therapy after resection in patients with hepatocellular carcinoma could prolong overall survival and recurrence-free survival and reduce recurrence rates without intolerable side effects. However, more evidence is needed before reaching a definitive conclusion.
Val50Met hereditary transthyretin amyloidosis: not just a medical problem, but a psychosocial burden
Authors: González-Moreno Juan , Gaya-Barroso Aina , Losada-López Inés , Rodríguez Adrián , Bosch-Rovira Teresa , Ripoll-Vera Tomás , Usón Mercedes , Figuerola Antoni , Descals Cristina , Montalà Carles , Ferrer-Nadal María Asunción , Cisneros-Barroso Eugenia
Published: June 2021

Background

Hereditary transthyretin (TTR) amyloidosis (ATTRv) is a heterogeneous disease with a clinical presentation that varies according to geographical area and TTR mutation. The symptoms of Val50Met-ATTRv are mainly neuropathic and progress to complete disability and death in most untreated patients within 10 to 15 years of diagnosis. The neurological effects may also be accompanied by gastrointestinal impairment, cardiomyopathy, nephropathy and/or ocular deposition. The disease is thus associated with a high degree of patient disability. Accordingly, we aimed to describe the psychosocial burden associated with ATTRv in a group of patients, asymptomatic Val50Met carriers, relatives and caregivers in the endemic focus of the disease in Majorca via a survey addressing various aspects related to psychosocial burden. We performed a an observational, descriptive, cross-sectional and multicentre study in order to analyze the prevalence of self-reported impact of ATTRv disease upon their daily life. In addition to the self-knowledge, fear and burden related to the disease. The survey was disseminated during the regular follow up at the outpatient clinic of the Hospital Universitario Son Llàtzer and during the meetings organized by the Andrade’s Disease patients’ advocacy group from the Balearic Islands. These meetings were attended also by subjects followed up by the Hospital Universitario Son Espases and their caregivers and relatives. Survey was self-administrated. No intervention was done by the investigators. 85 subjects completed the survey: 61 carrying the TTR-V50M variant and 24 caregivers or relatives.

Results

Our study revealed that, although most of the population studied had had prior contact with ATTRv through affected relatives, there was still a lack of information regarding disease diagnosis. Fear of the genetic test result and psychological issues were common in our population. Moreover, the disease had a stronger impact on the daily life of our patients than that of our asymptomatic carriers. Autonomic symptoms were the main source of burden for relatives and caregivers.

Conclusion

Our survey results show high psychosocial burden associated with Val50Met-ATTRv in our area.
Kinetic modeling of phosphorylase-catalyzed iterative β-1,4-glycosylation for degree of polymerization-controlled synthesis of soluble cello-oligosaccharides
Authors: Klimacek Mario , Zhong Chao , Nidetzky Bernd
Published: June 2021

Background

Cellodextrin phosphorylase (CdP; EC 2.4.1.49) catalyzes the iterative β-1,4-glycosylation of cellobiose using α-d-glucose 1-phosphate as the donor substrate. Cello-oligosaccharides (COS) with a degree of polymerization (DP) of up to 6 are soluble while those of larger DP self-assemble into solid cellulose material. The soluble COS have attracted considerable attention for their use as dietary fibers that offer a selective prebiotic function. An efficient synthesis of soluble COS requires good control over the DP of the products formed. A mathematical model of the iterative enzymatic glycosylation would be important to facilitate target-oriented process development.

Results

A detailed time-course analysis of the formation of COS products from cellobiose (25 mM, 50 mM) and α-d-glucose 1-phosphate (10–100 mM) was performed using the CdP from Clostridium cellulosi. A mechanism-based, Michaelis–Menten type mathematical model was developed to describe the kinetics of the iterative enzymatic glycosylation of cellobiose. The mechanistic model was combined with an empirical description of the DP-dependent self-assembly of the COS into insoluble cellulose. The hybrid model thus obtained was used for kinetic parameter determination from time-course fits performed with constraints derived from initial rate data. The fitted hybrid model provided excellent description of the experimental dynamics of the COS in the DP range 3–6 and also accounted for the insoluble product formation. The hybrid model was suitable to disentangle the complex relationship between the process conditions used (i.e., substrate concentration, donor/acceptor ratio, reaction time) and the reaction output obtained (i.e., yield and composition of soluble COS). Model application to a window-of-operation analysis for the synthesis of soluble COS was demonstrated on the example of a COS mixture enriched in DP 4.

Conclusions

The hybrid model of CdP-catalyzed iterative glycosylation is an important engineering tool to study and optimize the biocatalytic synthesis of soluble COS. The kinetic modeling approach used here can be of a general interest to be applied to other iteratively catalyzed enzymatic reactions of synthetic importance.
Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis
Authors: Liu Yiping , Su Yan-Yan , Yang Qian , Zhou Tianbiao
Published: June 2021

Renal fibrosis commonly leads to glomerulosclerosis and renal interstitial fibrosis and the main pathological basis involves tubular atrophy and the abnormal increase and excessive deposition of extracellular matrix (ECM). Renal fibrosis can progress to chronic kidney disease. Stem cells have multilineage differentiation potential under appropriate conditions and are easy to obtain. At present, there have been some studies showing that stem cells can alleviate the accumulation of ECM and renal fibrosis. However, the sources of stem cells and the types of renal fibrosis or renal fibrosis models used in these studies have differed. In this review, we summarize the pathogenesis (including signaling pathways) of renal fibrosis, and the effect of stem cell therapy on renal fibrosis as described in preclinical and clinical studies. We found that stem cells from various sources have certain effects on improving renal function and alleviating renal fibrosis. However, additional clinical studies should be conducted to confirm this conclusion in the future.
Intra-iliac bone marrow injection as a novel alternative to intra-tibial inoculation in rat model
Authors: Khattab Marwa S. , AbuBakr Huda O. , El Iraqi Kassem G. , AbdElKader Naglaa A. , Kamel Mervat M. , Salem Khaled Hamed , Steitz Julia , Afify Mamdouh
Published: June 2021

Background

Intra-bone marrow injection (IBMI) in rats is adopted in many studies for stem cell and hematopoietic cell transplantation. IBMI in the tibia or the femur results in severe distress to the animal. Therefore, this study aims to evaluate intra-iliac injections as an alternative approach for IBMI.

Methods

Twenty-seven Sprague Dawley rats were assigned into 3 groups, 9 rats each, for 4 weeks. The control group rats were not injected. Tibia group rats were injected intra-tibial and the iliac group rats were injected intra-iliac with saline. Behavioral, radiological, histopathological, and stress evaluation was performed. Total bilirubin, cortisol, and insulin-like growth factor-1 (IGF1) were measured.

Results

Behavioral measurements revealed deviation compared to control, in both injected groups, on the 1st and 2nd week. By the 3rd week, it was equivalent to control in the iliac group only. Bilirubin and cortisol levels were increased by intra-tibial injection compared to intra-iliac injection. The IGF-1 gene expression increased compared to control at 1st and 2nd weeks in intra-iliac injection and decreased by intra-tibial injection at 2nd week. The thickness of the iliac crest was not different from the control group, whereas there were significant differences between the control and tibia groups. Healing of the iliac crest was faster compared to the tibia. In the 3rd week, the tibia showed fibrosis at the site of injection whereas the iliac crest showed complete bone reconstruction.

Conclusion

Intra-iliac injections exert less distress on animals, and by 3 weeks, they regained their normal activity in comparison to intra-tibial injections.
One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study
Authors: Lu Jing , Shen Shan-mei , Ling Qing , Wang Bin , Li Li-rong , Zhang Wei , Qu Duo-duo , Bi Yan , Zhu Da-long
Published: June 2021

Background

The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D.

Methods

This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses.

Results

After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed.

Conclusion

One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone.

Trial registration

ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/
Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway
Authors: Lin Zhixiao , Zhao Congying , Lei Zhanjun , Zhang Yuheng , Huang Rong , Lin Bin , Dong Yuchen , Zhang Hao , Li Jinqing , Li Xueyong
Published: June 2021

Background

Epidermal stem cells (EpSCs) play a vital role in wound healing and skin renewal. Although biomaterial scaffolds have been used for transplantation of EpSCs in wound healing, the ex vivo differentiation of EpSCs limits their application.

Methods

To inhibit the differentiation of EpSCs and maintain their stemness, we developed an electrospun polycaprolactone (PCL)+cellulose acetate (CA) micro/nanofiber for the culture and transplantation of EpSCs. The modulation effect on EpSCs of the scaffold and the underlying mechanism were explored. Liquid chromatography-tandem mass spectrometry for label-free quantitative proteomics was used to analyze proteomic changes in EpSCs cultured on scaffolds. In addition, the role of transplanted undifferentiated EpSCs in wound healing was also studied.

Results

In this study, we found that the PCL+CA micro/nanofiber scaffold can inhibit the differentiation of EpSCs through YAP activation-mediated inhibition of the Notch signaling pathway. Significantly differentially expressed proteomics was observed in EpSCs cultured on scaffolds and IV collagen-coated culture dishes. Importantly, differential expression levels of ribosome-related proteins and metabolic pathway-related proteins were detected. Moreover, undifferentiated EpSCs transplanted with the PCL+CA scaffold can promote wound healing through the activation of the Notch signaling pathway in rat full-thickness skin defect models.

Conclusions

Overall, our study demonstrated the role of the PCL+CA micro-nanofiber scaffold in maintaining the stemness of EpSCs for wound healing, which can be helpful for the development of EpSCs maintaining scaffolds and exploration of interactions between biomaterials and EpSCs.