bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental study on creep properties prediction of reed bales based on SVR and MLP
Authors: Li Jixia , Zhang Lixin , Huang Guangdi , Wang Huan , Jiang Youzhong
Published: October 2021

Background

Reed has high lignin content, wide distribution and low cost. It is an ideal raw material for replacing wood in the paper industry. Reeds are rich in resources, but the density of reeds is low, leading to high transportation and storage costs. This paper aims to study the compression process of reeds and the creep behaviour of compressed reeds, and provide theoretical guidance for the reed compressor management, bundling equipment and the stability of compressed reed bales.

Results

We have established a multi-layer perceptron network prediction model for the creep characteristics of reeds, and the prediction rate R2of this model is greater than 0.997. The constitutive equation, constitutive coefficient and creep quaternary model of the reed creep process were established by using the prediction model. The creep behaviour of the reed bale is positively correlated with the initial maximum compressive stress (σ0). During the creep of the reed, the elastic power and the viscous resistance restrict each other. The results show that the proportion of elastic strain in the initial stage is the largest, and gradually decreases to 99.19% over time. The viscoelastic strain increases rapidly with time, then slowly increases, and finally stabilizes to 0.69%, while the plastic strain accounts for the proportion of the total strain. The specific gravity of the reed increases linearly with the increase of creep time, and finally accounts for 0.39%, indicating that as time increases, the damage of the reed's own structure gradually increases.

Conclusions

We studied the relationship between the strain and time of the reed and the strain and creep behaviour of the reed bag under different holding forces under constant force. It is proved that the multi-layer perceptron network is better than the support vector machine regression in predicting the characteristics of reed materials. The three stages of elasticity, viscoelasticity and plasticity in the process of reed creep are analysed in detail. This article opens up a new way for using machine learning methods to predict the mechanical properties of materials. The proposed prediction model provides new ideas for the characterization of material characteristics.
Implementation of innovative medical technologies in German inpatient care: patterns of utilization and evidence development
Authors: Dreger Marie , Eckhardt Helene , Felgner Susanne , Ermann Hanna , Lantzsch Hendrikje , Rombey Tanja , Busse Reinhard , Henschke Cornelia , Panteli Dimitra
Published: October 2021

Background

Innovative medical technologies are commonly associated with positive expectations. At the time of their introduction into care, there is often little evidence available regarding their benefits and harms. Accordingly, some innovative medical technologies with a lack of evidence are used widely until or even though findings of adverse events emerge, while others with study results supporting their safety and effectiveness remain underused. This study aims at examining the diffusion patterns of innovative medical technologies in German inpatient care between 2005 and 2017 while simultaneously considering evidence development.

Methods

Based on a qualitatively derived typology and a quantitative clustering of the adoption curves, a representative sample of 21 technologies was selected for further evaluation. Published scientific evidence on efficacy/effectiveness and safety of the technologies was identified and extracted in a systematic approach. Derived from a two-dimensional classification according to the degree of utilization and availability of supportive evidence, the diffusion patterns were then assigned to the categories “Success” (widespread/positive), “Hazard” (widespread/negative), “Overadoption” (widespread/limited or none), “Underadoption” (cautious/positive), “Vigilance” (cautious/negative), and “Prudence” (cautious/limited or none).

Results

Overall, we found limited evidence on the examined technologies regarding both the quantity and quality of published randomized controlled trials. Thus, the categories “Prudence” and “Overadoption” together account for nearly three-quarters of the years evaluated, followed by “Success” with 17%. Even when evidence is available, the transfer of knowledge into practice appears to be inhibited.

Conclusions

The successful implementation of safe and effective innovative medical technologies into practice requires substantial further efforts by policymakers to strengthen systematic knowledge generation and translation. Creating an environment that encourages the conduct of rigorous studies, promotes knowledge translation, and rewards innovative medical technologies according to their added value is a prerequisite for the diffusion of valuable health care.
Benefit of chemotherapy based on platinum with definitive radiotherapy in older patients with locally advanced esophageal squamous cell carcinoma
Authors: Wu Haishan , Yu Yilin , Zheng Qunhao , Liu Tianxiu , Wu Yahua , Wang Zhiping , Zheng Hongying , Liu Lingyun , Li Jiancheng
Published: October 2021

Objective

There is still no definitely therapeutic evidence of a beneficial effect of chemotherapy with radiotherapy for older patients with esophageal squamous cell carcinoma (ESCC). We aim to determine the influence of chemoradiotherapy (CRT) and radiotherapy (RT) alone in patients aged 65 years or older with locally advanced ESCC.

Methods

We retrospectively analyzed 581 ESCC patients who underwent CRT and RT alone. Univariate and multivariate Cox regression analysis was used to analyze the impact of clinical factors on long‐term overall survival (OS) and progression-free survival (PFS). Finally, we compared the toxicity rates of these patients.

Results

The median OS and PFS of the overall population were 23.2 months (2.0–162.6 months) and 18.6 months (1.1–159.6 months). Multivariate Cox regression analysis showed that chemotherapy (p < 0.05), tumor thickness (p < 0.01), and N stage (p < 0.05) were independent prognostic factors associated with both OS and PFS. In the chemotherapy subgroup, patients who received 2–8 cycles of chemotherapy had better OS than those who received 1 cycle (p = 0.015). The results also revealed that the CRT group has better OS and PFS than RT alone group for patients aged 65–74 years (both p < 0.01). However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone (both p > 0.05). Besides, higher staged ESCC has the inferior OS and PFS than lower staged ESCC for patients received RT alone and aged 65–74 years (both p < 0.05). Finally, there were significantly more severe hematologic toxicities in the CRT group than in those treated with RT alone in this study (p < 0.001).

Conclusions

The present study suggested that CRT for locally advanced ESCC in patients aged 65 years or older had a significant benefit over RT alone in terms of OS and PFS. However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone. CRT should be performed with special attention in patients aged 75 years or older.
Incidence and risk factors associated with human albumin administration following total joint arthroplasty: a multicenter retrospective study
Authors: Zhang Shaoyun , Si Haibo , Xie Jinwei , Wu Yuangang , Hu Qinsheng , Zeng Yi , Pei Fuxing , Shen Bin
Published: October 2021

Background

Enhanced recovery after surgery (ERAS) program advocates implementation of perioperative goal-directed fluid therapy and reduced application of colloidal fluids. It should be used reasonably selectively in high-risk patients despite the clear efficacy of human albumin (HA). Therefore, it is vital to identify the risk factors for the use of HA. This study aims to determine the incidence and risk factors of HA administration in patients undergoing total hip or knee arthroplasty (THA, TKA).

Methods

We identified patients undergoing THA or TKA in multiple institutions from 2014 to 2016 and collected patient demographics and perioperative variables. The criterion of HA administration was defined as a postoperative albumin level < 32 g/L or 32 to 35 g/L for at-risk patients. We compared 14 variables between patients who received HA administration and those who did not after stratification by the preoperative albumin (pre-ALB) level. Multivariable regressions identified the independent risk factors associated with HA administration.

Results

In total, 958 (20.3%) of 4713 patients undergoing THA and 410 (9.7%) of 4248 patients undergoing TKA received HA administration. In addition to pre-ALB < 35 g/L, preoperative anemia (odds ratio [OR] 2.12, P = 0.001; OR 1.39, P < 0.001) and drain use (OR 3.33, P = 0.001; OR 4.25, P < 0.001) were also independent risk factors for HA administration after THA regardless pre-ALB < 35 g/L or not, and patients undergoing TKA diagnosed of rheumatoid arthritis or ankylosing spondylitis tended to receive HA administration regardless pre-ALB < 35 g/L or not (OR 3.67, P = 0.002; OR 2.06, P < 0.001).

Conclusions

The incidence of HA administration was high in patients undergoing THA or TKA, and several variables were risk factors for HA administration. This finding may aid surgeons in preoperatively identifying patients requiring HA administration and optimizing perioperative managements.
Intra-articular injection of loaded sPL sustained-release microspheres inhibits osteoarthritis and promotes cartilaginous repairs
Authors: Li Jiyou , Liu Ning , Huang Zhipeng , Wang Wantao , Hou Donghua , Wang Wenbo
Published: October 2021

Background

Osteoarthritis is a chronic inflammatory disease of the joints associated with significant morbidity and lower quality of life. Current treatment strategies focus on reducing cartilage degeneration but fail to restore their proliferative ability. Super-activated platelet lysate (sPL) is an enhanced form of platelet-rich plasma that can be easily inactivated. The purpose of this study is to evaluate whether sPL-loaded PLGA/chitosan/gelatin microspheres can prevent and treat osteoarthritis.

Methods

Features of biological microspheres were detected by SEM and ELISA. Osteoarthritis chondrocytes were co-cultured with hydrogel loaded with sPL. The effect of biological microspheres on chondrocyte proliferation was evaluated using a CCK-8 cell proliferation test. Cell morphology and cell necrosis were measured with a microscope. The gene expression levels of cartilage-related markers type 2 collagen, aggrecan (ACAN), and SRY type high mobility group box-9 (SOX9) were determined by real-time quantitative polymerase chain reaction (Rt-PCR). A rat osteoarthritis model was established. Micro-CT was used to characterize cartilaginous changes after the injection of biological microspheres. Histopathological HE staining, Safranin-O Fast Green staining and staining scores, type II collagen staining, and proteoglycan staining were used to evaluate the degree of cartilaginous repair.

Results

Biological microspheres were able to continuously release biological factors. Exposure to loading sPL microspheres significantly increased chondrocyte proliferation, reduced cell necrosis, and increased the expression of cartilage markers type 2 collagen, ACAN, and SOX9 in osteoarthritic chondrocytes. In vivo experiments found that biological microspheres also smoothen cartilage surfaces, promote the expression of proteoglycan and type 2 collagen while also increasing cartilaginous integrity as evaluated using Safranin-O Fast Green staining.

Conclusions

PLGA/chitosan/gelatin hydrogel loaded with sPL is a promising tool for effective and non-invasive articular cartilage repair in osteoarthritis.

Graphic abstract

Biological microspheres loaded with sPL release various biological factors to promote chondrocyte proliferation and upregulate chondrocyte functionalization genes (SOX9, CoX II, ACAN), leading to an overall enhanced cartilaginous matrix.
Doxorubicin inhibits osteosarcoma progression by regulating circ_0000006/miR-646/ BDNF axis
Authors: Amuti Abulimiti , Liu Dehu , Maimaiti Ayiguli , Yu Yao , Yasen Yalikun , Ma Haoguang , Li Rui , Deng Shurong , Pang Fei , Tian Youliang
Published: October 2021

Background

Osteosarcoma (OS) is the most common aggressive bone tumor in children and teenagers. Doxorubicin (DOX) is a chemotherapeutic drug for OS. This study aims to reveal the effects and underneath mechanism of DOX treatment in OS progression.

Methods

The expression of circular_0000006 (circ_0000006), microRNA-646 (miR-646) and brain-derived neurotrophic factor (BDNF) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF protein expression was determined by western blot. Cell proliferation was illustrated by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were revealed by transwell migration and wound-healing assays and transwell invasion assay, respectively. Cell apoptosis was demonstrated by flow cytometry analysis. The binding relationship of miR-646 and circ_0000006 or BDNF was predicted by circRNA interactome and targetscan online database, respectively, and verified by dual-luciferase reporter assay. The effects of circ_0000006 knockdown on tumor growth in vivo were manifested by in vivo tumor formation assay.

Results

Circ_0000006 expression and the mRNA and protein levels of BDNF were dramatically upregulated, and miR-646 expression was effectively downregulated in OS tissues or cells compared with control groups. Circ_0000006 expression and BDNF protein expression were lower, and miR-646 expression was higher in DOX treatment groups than in control groups in OS cells. Circ_0000006 knockdown repressed cell proliferation, migration and invasion, whereas promoted cell apoptosis under DOX treatment in OS cells; however, these effects were attenuated by miR-646 inhibitor. Additionally, circ_0000006 sponged miR-646 to bind to BDNF. Circ_0000006 silencing suppressed tumor growth in vivo.

Conclusion

Circ_0000006 knockdown promoted DOX-mediated effects on OS development by miR-646/BDNF pathway, which provided a theoretical basis in treating OS with DOX.
Role of a new age-adjusted D-dimer cutoff value for preoperative deep venous thrombosis exclusion in elderly patients with hip fractures
Authors: Zhang Kexin , Zhu Yanbin , Tian Yunxu , Tian Miao , Li Xiuting , Zhang Yingze
Published: October 2021

Objective

This study aimed to describe the characteristics of plasma D-dimer level with increasing age and establish a new age-adjusted D-dimer cutoff value for excluding preoperative lower limb deep vein thrombosis (DVT) in elderly patients with hip fractures.

Methods

This was a retrospective study of elderly patients who presented with acute hip fracture in our institution between June 2016 and June 2019. All patients underwent D-dimer test and duplex ultrasound. Patients were divided into six 5-year-apart age groups. The optimal cutoff value for each group was calculated by using receiver operating characteristic (ROC) curves, whereby the new age-adjusted D-dimer cutoff value was determined. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were calculated and compared when different D-dimer cutoff values were applied, i.e., conventional 0.5 mg/L, previously well-established age-adjusted cutoff value (age × 0.01 mg/L) and the new age-adjusted D-dimer cutoff value herein.

Results

There were 2759 patients included, 887 males and 1872 females, with an average age of 78 years. In total, 280 patients were diagnosed with preoperative DVT. The optimal cutoff values for the six age groups were 0.715 mg/L, 1.17 mg/L, 1.62 mg/L, 1.665 mg/L, 1.69 mg/L and 1.985 mg/L, respectively, and the calculated age-adjusted coefficient was 0.02 mg/L. With this new coefficient applied, the specificity was 61%, clearly higher than those for conventional threshold (0.5 mg/L, 37%) or previously established age-adjusted D-dimer threshold (age × 0.01 mg/L, 22%). In contrast, the sensitivity was lower than that (59% vs 85% or 77%) when D-dimer threshold of 0.5 mg/L or age-adjusted cutoff value (age × 0.01 mg/L) was used. The other indexes as PPV (15%, 11% and 12%) and NPV (93%, 93% and 94%) were comparable when three different D-dimer thresholds were applied.

Conclusions

We developed a new age-adjusted D-dimer cutoff value (age × 0.02 mg/L) for a specified high-risk population of patients aged 65 years or older with hip fractures, and demonstrated the improved utility of the D-dimer test for exclusion of DVT. This formula can be considered for use in elderly hip fracture patients who meet the applicable standards as preoperative DVT screening, after its validity is confirmed by more well-evidenced studies.
Investigation of the role of the miR17-92 cluster in BMP9-induced osteoblast lineage commitment
Authors: Zhang Yunyuan , Jing Xuran , Li Zhongzhu , Tian Qingwu , Wang Qing , Chen Xian
Published: October 2021

Background

Bone morphogenetic protein 9 (BMP9) has been identified as a crucial inducer of osteoblastic differentiation in mesenchymal stem cells (MSCs). Although microRNAs (miRNAs) are known to play a role in MSC osteogenesis, the mechanisms of action of miRNAs in BMP9-induced osteoblastic differentiation remain poorly understood.

Methods

In this study, we investigate the possible role of the miR17-92 cluster in the BMP9-induced osteogenic differentiation of MSCs by using both in vitro and in vivo bone formation assays.

Results

The results show that miR-17, a member of the miR17-92 cluster, significantly impairs BMP9-induced osteogenic differentiation. This impairment is effectively rescued by a miR-17 sponge, an antagomiR sequence against miR-17. Using TargetScan and the 3′-untranslated region luciferase reporter assays, we show that the direct target of miR-17 is the retinoblastoma gene (RB1), a gene that is pivotal to osteoblastic differentiation. We also confirm that RB1 is essential for the miR-17 effects on osteogenesis.

Conclusion

Our results indicate that miR-17 expression impairs normal osteogenesis by downregulating RB1 expression and significantly inhibiting the function of BMP9.
S2-alar-iliac screw and S1 pedicle screw fixation for the treatment of non-osteoporotic sacral fractures: a finite element study
Authors: Zheng Jianxiong , Feng Xiaoreng , Xiang Jie , Liu Fei , Leung Frankie K. L. , Chen Bin
Published: October 2021

Background

Five different sacral fracture fixation methods were compared using finite element (FE) analysis to study their biomechanical characteristics.

Methods

Denis type I sacral fractures were created by FE modeling. Five different fixation methods for the posterior pelvic ring were simulated: sacroiliac screw (SIS), lumbopelvic fixation (LPF), transiliac internal fixator (TIFI), S2-alar-iliac (S2AI) screw and S1 pedicle screw fixation (S2AI-S1) and S2AI screw and contralateral S1 pedicle screw fixation (S2AI-CS1). Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending and left twisting, respectively. Vertical stiffness, relative displacement and change in relative displacement were recorded and analyzed.

Results

As predicted by the FE model, the vertical stiffness of the five groups in descending order was S2AI-S1, SIS, S2AI-CS1, LPF and TIFI. In terms of relative displacement, groups S2AI-S1 and S2AI-CS1 displayed a lower mean relative displacement, although group S2AI-CS1 exhibited greater displacement in the upper sacrum than group S2AI-S1. Group SIS displayed a moderate mean relative displacement, although the displacement of the upper sacrum was smaller than the corresponding displacement in group S2AI-CS1, while groups LPF and TIFI displayed larger mean relative displacements. Finally, in terms of change in relative displacement, groups TIFI and LPF displayed the greatest fluctuations in their motion, while groups SIS, S2AI-S1 and S2AI-CS1 displayed smaller fluctuations.

Conclusion

Compared with SIS, unilateral LPF and TIFI, group S2AI-S1 displayed the greatest biomechanical stability of the Denis type I sacral fracture FE models. When the S1 pedicle screw insertion point on the affected side is damaged, S2AI-CS1 can be used as an appropriate alternative to S2AI-S1.
Four-branched graft inversion technique for the distal anastomosis in acute aortic dissection
Authors: Zou Yu , Teng Peng , Ma Liang
Published: October 2021

Background

Distal anastomosis bleeding is an issue during total arch replacement with the frozen elephant trunk technique. We used the 4-branched graft inversion technique for the distal anastomosis in acute aortic dissection. The aim was to evaluate the feasibility and benefits of the technique used during the frozen elephant trunk procedure for acute aortic dissection.

Methods

From January 2017 to July 2019, 109 patients underwent total arch replacement for type A acute aortic dissections. Patients were divided according to the technique used for the distal anastomosis as follows: group G (n = 57; 4-branched graft inversion technique) and group C (n = 52; conventional method with Teflon felt). The postoperative variables were analysed.

Results

The hospital mortality rate was 9.2% (10/109). The mean cardiopulmonary bypass, cardiac arrest, and circulatory arrest times were 234.95 ± 71.88 min, 168.25 ± 61.33 min, and 39.19 ± 9.45 min, respectively. The circulatory arrest and cardiac arrest times were shorter in the graft inversion group than in the conventional group (36.46 ± 7.88 min vs. 42.19 ± 10.17 min, P = 0.001 and 156.21 ± 55.99 min vs. 181.44 ± 64.68 min, P = 0.031, respectively). There were 7 cases of stroke (6.4%) and 5 cases of paraplegia (4.6%). Additionally, 13 patients (11.9%) required temporary continuous renal replacement therapy. Respiratory failure occurred in 19 patients (17.4%). There were no significant differences in postoperative complications between the two groups.

Conclusions

The 4-branched graft inversion technique provides effective and confirmed haemostasis during total aortic arch replacement using the frozen elephant trunk procedure.
Effect of ventilation strategy during cardiopulmonary bypass on postoperative pulmonary complications after cardiac surgery: a randomized clinical trial
Authors: Zhang Meng-Qiu , Liao Yu-Qi , Yu Hong , Li Xue-Fei , Shi Wei , Jing Wei-Wei , Wang Zai-Li , Xu Yi , Yu Hai
Published: October 2021

Background

To determine whether maintaining ventilation during cardiopulmonary bypass (CPB) with a different fraction of inspired oxygen (FiO2) had an impact on the occurrence of postoperative pulmonary complications (PPCs).

Methods

A total of 413 adult patients undergoing elective cardiac surgery with CPB were randomly assigned into three groups: 138 in the NoV group (received no mechanical ventilation during CPB), 138 in the LOV group (received a tidal volume (VT) of 3–4 ml/kg of ideal body weight with the respiratory rate of 10–12 bpm, and the positive end-expiratory pressure of 5–8 cmH2O during CPB; the FiO2 was 30%), and 137 in the HOV group (received the same ventilation parameters settings as the LOV group while the FiO2 was 80%).

Results

The primary outcomes were the incidence and severity of PPCs during hospitalization. The composite incidence of PPCs did not significantly differ between the NoV (63%), LOV (49%) and HOV (57%) groups (P = 0.069). And there was also no difference regarding the incidence of PPCs between the non-ventilation (NoV) and ventilation (the combination of LOV and HOV) groups. The LOV group was observed a lower proportion of moderate and severe pulmonary complications (grade ≥ 3) than the NoV group (23.1% vs. 44.2%, P = 0.001).

Conclusion

Maintaining ventilation during CPB did not reduce the incidence of PPCs in patients undergoing cardiac surgery.

Trial registration: Chinese Clinical Trial Registry ChiCTR1800015261. Prospectively registered 19 March 2018. http://www.chictr.org.cn/showproj.aspx?proj=25982
Risk factors for 30-day mortality in patients who received DeBakey type I aortic dissection repair surgery
Authors: Wang Zhigang , Chen Tao , Ge Pingping , Ge Min , Lu Lichong , Zhang Lifang , Wang Dongjin
Published: October 2021

Objective

This study aimed to identify risk factors for 30-day mortality in patients who received DeBakey type I aortic dissection (AD) repair surgery.

Methods

A total of 830 consecutive patients who received acute DeBakey type I AD surgery between 2014 and 2019 were included in the study. The associations between 30-day mortality and perioperative parameters were examined in order to identify risk factors.

Results

Our data suggested that the overall 30-day mortality rate of all enrolled patients was 11.7%. Unsurprisingly, non-survivors were older and more frequently accompanied with histories of cardiovascular diseases. For intraoperative parameters, the prevalence of coronary artery bypass grafting and cardiopulmonary bypass times were increased in non-survivors. In addition, acute kidney injury (AKI), dialysis, stroke, and deep sternal wound infection were more commonly seen among non-survivors. The multivariate logistic regression analysis suggested that cardiovascular disease history, preoperative D-dimer level, drainage volume 24 h after surgery, and postoperative AKI were independent risk factors for 30-day mortality after DeBakey type I aortic dissection repair surgery.

Conclusions

Our study demonstrated that cardiovascular disease history, preoperative D-dimer level, drainage volume 24 h after surgery as well as postoperative AKI were risk factors for 30-day mortality after DeBakey type I aortic dissection repair surgery.
Evaluation of the long-term treatment effects of intravenous idursulfase in patients with mucopolysaccharidosis II (MPS II) using statistical modeling: data from the Hunter Outcome Survey (HOS)
Authors: Muenzer Joseph , Botha Jaco , Harmatz Paul , Giugliani Roberto , Kampmann Christoph , Burton Barbara K.
Published: October 2021

Background

Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare, life-limiting lysosomal storage disease caused by deficient iduronate-2-sulfatase activity. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase can stabilize or improve many somatic manifestations, but there remains a need for further analysis of long-term treatment outcomes. Using data from patients with MPS II enrolled in the Hunter Outcome Survey (HOS), mixed modeling was performed to evaluate and predict the effects of IV idursulfase treatment on selected clinical parameters for up to 8 years following treatment start. The modeling population comprised male patients followed prospectively in HOS who had received IV idursulfase for at least 5 years and who had data available for two or more time points (at least one post-ERT). Age at ERT start and time since ERT start were included as covariates.

Results

In total, 481 patients were eligible for inclusion in at least one model. At 8 years post-ERT start, improvement from baseline was predicted for each age group (< 18 months, 18 months to < 5 years and ≥ 5 years at treatment start) in the following parameters: mean urinary glycosaminoglycan levels (percentage changes of > –75% in each group), mean left ventricular mass index (decreases of ~ 1 g/m2) and mean palpable liver size (decreases of > 2 cm). Improvements in mean 6-min walk test distance (increase of > 50 m) and stabilization in percent predicted forced vital capacity and forced expiratory volume in 1 s (decreases of ~ 4 and ~ 9 percentage points, respectively) at 8 years post-ERT start were predicted for patients aged ≥ 5 years at ERT start (these assessments are unsuitable for patients aged < 5 years). Predicted changes over time were similar across the three age groups; however, overall outcomes were most favorable in children aged < 18 months at ERT start.

Conclusions

These findings suggest that the previously reported positive effects of IV idursulfase on the somatic manifestations of MPS II are predicted to be maintained for at least 8 years following ERT initiation and highlight the value of statistical modeling to predict long-term treatment outcomes in patients with rare diseases.
Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease
Authors: Cleanthous Sophie , Mork Ann-Christin , Regnault Antoine , Cano Stefan , Kaminski Henry J. , Morel Thomas
Published: October 2021

Background

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease, characterised by fluctuating muscle weakness which makes it challenging to assess symptom severity. Mixed methods psychometrics (MMP), which combines evidence from qualitative research and modern psychometrics, is a versatile approach to the development of patient-centred outcome measures (PCOM) in the context of rare disease. Our objective was to develop the MG Symptom patient-reported outcome (PRO) to assess key aspects of MG severity from the patient perspective.

Methods

We used MMP to develop a novel PRO instrument in a multi-step process. An initial conceptual model for MG patient experience was developed and expanded based on preliminary literature review and two waves of concept elicitation interviews with people with MG (Step 1). Based on this, the novel PRO instrument, the MG Symptoms PRO, was drafted. The draft instrument was refined by combining qualitative and quantitative data collected in a Phase 2 clinical study (Step 2).

Results

Findings from the literature review and concept elicitation interviews (n = 96) indicated that patient experience in MG includes proximal muscle weakness symptoms related to several body parts, along with muscle weakness fatigability and general fatigue. Then, a set of 42 items across five scales (ocular-, bulbar-, and respiratory muscle weakness, physical fatigue, and muscle weakness fatigability) was developed. Qualitative evidence endorsed its relevance, clarity, and ease of completion; quantitative analysis with Rasch measurement theory methods demonstrated strong measurement properties, including good targeting and high reliability. Classical test theory analyses showed adequate reliability of the instrument and mild to moderate correlations with other widely used MG-specific outcome measures.

Conclusions

The MG Symptoms PRO has potential to be used both to measure treatment benefit in clinical trials and monitor symptom severity in clinical practice. Its component scales were purposefully designed to stand alone, enhancing interpretability of scores given the heterogeneity of MG, and enabling modular use. Compared with existing MG PROs, it contains more detailed assessments of muscle weakness and muscle weakness fatigability symptoms, which are of key importance to people with MG. The MMP approach used may serve as a case study for developing PCOMs across rare disease indications.
Efficacy of rikkosan for primary burning mouth syndrome: a retrospective study
Authors: Hato Hiroyuki , Sakata Ken-ichiro , Sato Jun , Asaka Takuya , Ohga Noritaka , Yamazaki Yutaka , Kitagawa Yoshimasa
Published: October 2021

Background

Burning mouth syndrome (BMS) is a chronic condition characterized by pain in the oral cavity. Kampo medicine is a traditional Japanese medical system that has its roots partly in ancient Chinese medicine. The purpose of this study is to evaluate the efficacy of rikkosan—a traditional Japanese herbal medicine (Kampo)—in the treatment of primary BMS.

Main body

A single-center retrospective study was conducted in 32 patients who were diagnosed with primary BMS and treated with rikkosan alone through gargling (2.5 g rikkosan dissolved in 50 mL hot water) three times daily. Patients were asked to evaluate their pain using a numerical rating scale (NRS) at first visit and after 1 month. One patient had stomatitis as a side effect after gargling with rikkosan, however, no side effects were observed in other patients. Overall NRS scores decreased significantly between the first visit (7.6 ± 2.7) and the 1-month visit (5.6 ± 2.8).

Conclusions

Rikkosan may be an effective treatment for primary BMS.
Targeting CD47 for cancer immunotherapy
Authors: Jiang Zhongxing , Sun Hao , Yu Jifeng , Tian Wenzhi , Song Yongping
Published: October 2021

Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (ST) and hematological malignancies. We summarized the CD47-related clinical research and analyzed the research trend both in the USA and in China. As of August 28, 2021, there are a total 23 related therapeutic agents with 46 clinical trials in the NCT registry platform. Among these trials, 29 are in ST, 14 in hematological malignancies and 3 in both solid tumor and hematological malignancy. The ST include gastric cancer, head and neck squamous cell carcinoma and leiomyosarcoma, while the hematological malignancies include non-Hodgkin's lymphoma, acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and chronic myeloid leukemia. Majority of the CD47-related clinical trials are at the early phases, such as 31 at phase I, 14 at phase II and 1 at phase III in the USA and 9, 6, 1, in China, respectively. The targets and spectrums of mechanism of action include 26 with mono-specific and 20 with bi-specific targets in the USA and 13 with mono-specific and 3 with bi-specific targets in China. The new generation CD47 antibodies have demonstrated promising results, and it is highly hopeful that some candidate agents will emerge and make into clinical application to meet the urgent needs of patients.
High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer
Authors: Böttger Franziska , Vallés-Martí Andrea , Cahn Loraine , Jimenez Connie R.
Published: October 2021

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and boosting immune response. Moreover, high-dose IVC is powerful as an adjuvant treatment for cancer, acting synergistically with many standard (chemo-) therapies, as well as a method for mitigating the toxic side-effects of chemotherapy. Despite the rationale and ample evidence, strong clinical data and phase III studies are lacking. Therefore, there is a need for more extensive awareness of the use of this highly promising, non-toxic cancer treatment in the clinical setting. In this review, we provide an elaborate overview of pre-clinical and clinical studies using high-dose IVC as anti-cancer agent, as well as a detailed evaluation of the main known molecular mechanisms involved. A special focus is put on global molecular profiling studies in this respect. In addition, an outlook on future implications of high-dose vitamin C in cancer treatment is presented and recommendations for further research are discussed.
An overview of FSH-FSHR biology and explaining the existing conundrums
Authors: Bhartiya Deepa , Patel Hiren
Published: October 2021

FSH was first identified in 1930 and is central to mammalian reproduction. It is indeed intriguing that despite being researched upon for about 90 years, there is still so much more to learn about FSH-FSHR biology. The purpose of this review is to provide an overview of current understanding of FSH-FSHR biology, to review published data on biological and clinical relevance of reported mutations, polymorphisms and alternately spliced isoforms of FSHR. Tissue-resident stem/progenitor cells in multiple adult tissues including ovaries, testes and uterus express FSHR and this observation results in a paradigm shift in the field. The results suggest a direct action of FSH on the stem cells in addition to their well-studied action on Granulosa and Sertoli cells in the ovaries and testes respectively. Present review further addresses various concerns raised in recent times by the scientific community regarding extragonadal expression of FSHR, especially in cancers affecting multiple organs. Similar population of primitive and pluripotent tissue-resident stem cells expressing FSHR exist in multiple adult tissues including bone marrow and reproductive tissues and help maintain homeostasis throughout life. Any dysfunction of these stem cells results in various pathologies and they also most likely get transformed into cancer stem cells and initiate cancer. This explains why multiple solid as well as liquid tumors express OCT-4 and FSHR. More research efforts need to be focused on alternately spliced FSHR isoforms.
Endogenous, tissue-resident stem/progenitor cells in gonads and bone marrow express FSHR and respond to FSH via FSHR-3
Authors: Bhartiya Deepa , Patel Hiren , Kaushik Ankita , Singh Pushpa , Sharma Diksha
Published: October 2021

Follicle stimulating hormone (FSH) is secreted by the anterior pituitary and acts on the germ cells indirectly through Granulosa cells in ovaries and Sertoli cells in the testes. Extragonadal action of FSH has been reported but is still debated. Adult tissues harbor two populations of stem cells including a reserve population of primitive, small-sized, pluripotent very small embryonic-like stem cells (VSELs) and slightly bigger, tissue-specific progenitors which include ovarian stem cells (OSCs) in ovaries, spermatogonial stem cells (SSCs) in testes, endometrial stem cells (EnSCs) in uterus and hematopoietic stem cells (HSCs) in the bone marrow. Data has accumulated in animal models showing FSHR expression on both VSELs and progenitors in ovaries, testes, uterus and bone marrow and eventually gets lost as the cells differentiate further. FSH exerts a direct action on the stem/progenitor cells via alternatively spliced FSHR-3 rather than the canonical FSHR-1. FSH stimulates VSELs to undergo asymmetrical cell divisions to self-renew and give rise to the progenitors that in turn undergo symmetrical cell divisions and clonal expansions followed by differentiation into specific cell types. Excessive self-renewal of VSELs results in cancer and this explains ubiquitous expression of embryonic markers including nuclear OCT-4 along with FSHR in cancerous tissues. Focus of this review is to compile published data to support this concept. FSHR expression in stem/progenitor cells was confirmed by immuno-fluorescence, Western blotting, in situ hybridization and by quantitative RT-PCR. Two different commercially available antibodies (Abcam, Santacruz) were used to confirm specificity of FSHR expression along with omission of primary antibody and pre-incubation of antibody with immunizing peptide as negative controls. Western blotting allowed detection of alternatively spliced FSHR isoforms. Oligoprobes and primers specific for Fshr-1 and Fshr-3 were used to study these alternately-sliced isoforms by in situ hybridization and their differential expression upon FSH treatment by qRT-PCR. To conclude, stem/progenitor cells in adult tissues express FSHR and directly respond to FSH via FSHR-3.These findings change the field of FSH-FSHR biology, call for paradigm shift, explain FSHR expression on cancer cells in multiple organsand provide straightforward explanations for various existing conundrums including extragonadal expression of FSHR.
Minimum acceptable diet and associated factors among children aged 6–23 months in Ethiopia
Authors: Abebe Haimanot , Gashu Molla , Kebede Aynalem , Abata Habtemariam , Yeshaneh Alex , Workye Haile , Adane Daniel
Published: October 2021

Introduction

The health and growth of children less than two years of age can be affected by the poor quality of complementary foods and poor feeding practices even with optimal breastfeeding. In Ethiopia, empirical evidence on the minimum acceptable diet and its associated factors is limited. Therefore, this study was aimed to assess the level of minimum acceptable diet and its associated factors among children aged 6–23 months in Addis Ababa Ethiopia.

Methods

An institution-based Cross-sectional study was conducted among a total of 575 mother-child pairs. A simple random sampling technique was used to recruit participants. For infant and young child feeding practices, the data collection tools were adapted from world health organizations’ standardized questionnaire which is developed in 2007. Data entry and analysis were performed using EPI data version 3.1 and SPSS version 20 respectively. Bivariable and multivariable logistic regression analyses were performed to determine predictor variables. Statistical significance was declared at p-value < 0.05.

Result

In this study, the level of minimum acceptable diet was found to be 74.6%.. About 90.6 and 80.2% of the children received minimum meal frequency and dietary diversity respectively. Having a husband secondary and above educational level [AOR = 4.789(95%CI:1.917–11.967)], being a housewife [AOR = 0.351(95% CI: 0.150–0.819)], having a history of more than three postnatal follow-ups [AOR = 2.616(95%CI:1.120–6.111], Having mothers age between 25 and 34 years [AOR = 2.051(95%CI:1.267–3.320)], being male child [AOR = 1.585(95%CI:1.052–2.388)] and having children age between 18 and 23 months [AOR = 3.026(95%CI:1.786–5.128)] were some of the factors significantly associated with a minimum acceptable diet.

Conclusion

In this study, the minimum acceptable diet among children aged 6–23 months was significantly associated with the educational status of the husband, mother’s occupation, history of postnatal follow-up, age of the mother, sex of the child, and age of the child. Thus, attention should be given to educating the father, empowering mothers to have a job, promoting gender equality of feeding, and counseling on the benefit of postnatal care visits. In addition, the ministry of health should work on educating and advocating the benefit of feeding the recommended minimum acceptable diet to break the intergenerational cycle of malnutrition.
Video Intervention Therapy for primary caregivers in a child psychiatry unit: a randomized feasibility trial
Authors: Leyton Fanny , Olhaberry Marcia , Morán Javier , De la Cerda Cecilia , León María José , Sieverson Catalina , Alfaro Ángela , Hernández Camila , Alvardo Rubén , Steele Howard
Published: October 2021

Background

During child psychiatry hospitalization, working with the families or attachment figures is a challenge, most of the children who are admitted to these units come from multi-problem families, with limited research in this area. Video feedback (VF) interventions have proved to be a powerful resource to promote parental and child well-being in small children and has been used with parents with a psychiatric condition. Parental Reflective Functioning (PRF) is one of the parental abilities that can be improved with VF and could be especially important in coping with conflict and negative emotions in older children. The aim of this study is to implement Video Intervention Therapy (VIT) to enhance PRF in primary caregivers of inpatient psychiatric children. As there is no published research using VF with parents of children with severe psychopathology in a hospitalized context. This report, then, becomes a much needed pilot study providing evidence for a larger randomized control trial (RCT).

Methods

The study is a single-center, two-arm feasibility randomized control trial with a qualitative component. Block randomization was done to generate a 2:1 allocation, leaving more participants in the intervention group. The intervention comprises four modules; every module has both one video-recorded play session and one VIT session (in a group setting) per week. Evaluation of the caregivers included assessments of PRF and well-being, and child assessment included parent-ratings and clinician-ratings of symptomatology and general functioning.

Results

Thirty participants were randomized; eligibility and recruitment rate were 70.6% and 83.3%, respectively. The compliance-to-intervention rate was 85% in the VIT group and 90% in the control group. All participants completed entry evaluation and 90% at the 3-month follow-up. The intervention was acceptable to participants and feasible for therapists to deliver. Outcome data must be treated with caution due to the small numbers involved, yet indicate that the VIT may have a positive effect in improving parental and child mental health outcomes.

Conclusions

VIT for primary caregivers of child inpatient children was feasible to deliver and acceptable for participants, therapist, and the staff unit involved; there is sufficient evidence to undertake a full-scale effectiveness RCT.

Trial registration

ClinicalTrials.govNCT03374904. Registered on 14 December 2017
Bridging Recovery Initiative Despite Gaps in Entry (BRIDGE): study protocol for a randomized controlled trial of a bridge clinic compared with usual care for patients with opioid use disorder
Authors: Marcovitz David E. , White Katie D. , Sullivan William , Limper Heather M. , Dear Mary Lynn , Buie Reagan , Edwards David A. , Chastain Cody , Kast Kristopher A. , Lindsell Christopher J. ,   Vanderbilt Learning Health System Investigators
Published: October 2021

Background

Patients with substance use disorders are overrepresented among general hospital inpatients, and their admissions are associated with longer lengths of stay and increased readmission rates. Amid the national opioid crisis, increased attention has been given to the integration of addiction with routine medical care in order to better engage such patients and minimize fragmentation of care. General hospital addiction consultation services and transitional, hospital-based “bridge” clinics have emerged as potential solutions. We designed the Bridging Recovery Initiative Despite Gaps in Entry (BRIDGE) trial to determine if these clinics are superior to usual care for these patients.

Methods

This single-center, pragmatic, randomized controlled clinical trial is enrolling hospitalized patients with opioid use disorder (OUD) who are initiating medication for OUD (MOUD) in consultation with the addiction consult service. Patients are randomized for referral to a co-located, transitional, multidisciplinary bridge clinic or to usual care, with the assignment probability being determined by clinic capacity. The primary endpoint is hospital length of stay. Secondary endpoints include quality of life, linkage to care, self-reported buprenorphine or naltrexone fills, rate of known recurrent opioid use, readmission rates, and costs. Implementation endpoints include willingness to be referred to the bridge clinic, attendance rates among those referred, and reasons why patients were not eligible for referral. The main analysis will use an intent-to-treat approach with full covariate adjustment.

Discussion

This ongoing pragmatic trial will provide evidence on the effectiveness of proactive linkage to a bridge clinic intervention for hospitalized patients with OUD initiating evidence-based pharmacotherapy in consultation with the addiction consult service.

Trial registration

ClinicalTrials.govNCT04084392. Registered on 10 September 2019. The study has been approved by the Vanderbilt Institutional Review Board. The current approved protocol is dated version May 12, 2021.