bluuebunny/crossref_metadata_2025 huggingface dataset:
Activated protein C has a regulatory role in factor VIII function
Authors: Wilhelm Amelia R. , Parsons Nicole A. , Samelson-Jones Benjamin J. , Davidson Robert J. , Esmon Charles T. , Camire Rodney M. , George Lindsey A.
Published: January 2021

Mechanisms thought to regulate activated factor VIII (FVIIIa) cofactor function include A2-domain dissociation and activated protein C (APC) cleavage. Unlike A2-domain dissociation, there is no known phenotype associated with altered APC cleavage of FVIII, and biochemical studies have suggested APC plays a marginal role in FVIIIa regulation. However, the in vivo contribution of FVIIIa inactivation by APC is unexplored. Here we compared wild-type B-domainless FVIII (FVIII-WT) recombinant protein with an APC-resistant FVIII variant (FVIII-R336Q/R562Q; FVIII-QQ). FVIII-QQ demonstrated expected APC resistance without other changes in procoagulant function or A2-domain dissociation. In plasma-based studies, FVIII-WT/FVIIIa-WT demonstrated dose-dependent sensitivity to APC with or without protein S, whereas FVIII-QQ/FVIIIa-QQ did not. Importantly, FVIII-QQ demonstrated approximately fivefold increased procoagulant function relative to FVIII-WT in the tail clip and ferric chloride injury models in hemophilia A (HA) mice. To minimize the contribution of FV inactivation by APC in vivo, a tail clip assay was performed in homozygous HA/FV Leiden (FVL) mice infused with FVIII-QQ or FVIII-WT in the presence or absence of monoclonal antibody 1609, an antibody that blocks murine PC/APC hemostatic function. FVIII-QQ again demonstrated enhanced hemostatic function in HA/FVL mice; however, FVIII-QQ and FVIII-WT performed analogously in the presence of the PC/APC inhibitory antibody, indicating the increased hemostatic effect of FVIII-QQ was APC specific. Our data demonstrate APC contributes to the in vivo regulation of FVIIIa, which has the potential to be exploited to develop novel HA therapeutics.
Monocytes in sarcoidosis are potent tumour necrosis factor producers and predict disease outcome
Authors: Lepzien Rico , Liu Sang , Czarnewski Paulo , Nie Mu , Österberg Björn , Baharom Faezzah , Pourazar Jamshid , Rankin Gregory , Eklund Anders , Bottai Matteo , Kullberg Susanna , Blomberg Anders , Grunewald Johan , Smed-Sörensen Anna
Published: January 2021

Background

Pulmonary sarcoidosis is an inflammatory disease characterised by granuloma formation and heterogeneous clinical outcome. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine contributing to granuloma formation and high levels of TNF have been shown to associate with progressive disease. Mononuclear phagocytes (MNPs) are potent producers of TNF and highly responsive to inflammation. In sarcoidosis, alveolar macrophages have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells, which are poorly studied in sarcoidosis, despite their central role in inflammation.

Objective

To determine the role of pulmonary monocyte-derived cells and dendritic cells during sarcoidosis.

Methods

We performed in-depth phenotypic, functional and transcriptomic analysis of MNP subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls. We followed the clinical development of patients and assessed how the repertoire and function of MNP subsets at diagnosis correlated with 2-year disease outcome.

Results

Monocytes/monocyte-derived cells were increased in blood and BAL of sarcoidosis patients compared to healthy controls. Interestingly, high frequencies of blood intermediate monocytes at time of diagnosis associated with chronic disease development. RNA sequencing analysis showed highly inflammatory MNPs in BAL of sarcoidosis patients. Furthermore, frequencies of BAL monocytes/monocyte-derived cells producing TNF without exogenous stimulation at time of diagnosis increased in patients that were followed longitudinally. In contrast to alveolar macrophages, the frequency of TNF-producing BAL monocytes/monocyte-derived cells at time of diagnosis was highest in sarcoidosis patients that developed progressive disease.

Conclusion

Our data show that pulmonary monocytes/monocyte-derived cells are highly inflammatory and can be used as a predictor of disease outcome in sarcoidosis patients.
Blood eosinophils on hospital admission for COPD exacerbation do not predict the recurrence of moderate and severe relapses
Authors: Csoma Balázs , Bikov András , Tóth Ferenc , Losonczy György , Müller Veronika , Lázár Zsófia
Published: January 2021

Background and objective

The relationship between hospitalisation with an eosinophilic acute exacerbation of COPD (AE-COPD) and future relapses is unclear. We aimed to explore this association by following 152 patients for 12 months after hospital discharge or until their first moderate or severe flare-up.

Methods

Patients hospitalised with AE-COPD were divided into eosinophilic and non-eosinophilic groups based on full blood count results on admission. All patients were treated with a course of systemic corticosteroid. The Cox proportional hazards model was used to study the association with the time to first re-exacerbation; a generalised linear regression model was applied to identify clinical variables related to the recurrence of relapses.

Results

We did not find a difference in the time to the next moderate or severe exacerbation between the eosinophilic (≥2% of total leukocytes and/or ≥200 eosinophils·µL−1, n=51, median (interquartile range): 21 (10–36) weeks) and non-eosinophilic groups (n=101, 17 (9–36) weeks, log-rank test: p=0.63). No association was found when other cut-off values (≥3% of total leukocytes and/or ≥300 eosinophils·µL−1) were used for the eosinophilic phenotype. However, the higher number of past severe exacerbations, a lower forced expiratory volume in 1 s (FEV1) at discharge and higher pack-years were related to shorter exacerbation-free time. According to a subgroup analysis (n=73), 48.1% of patients with initial eosinophilic exacerbations had non-eosinophilic relapses on readmission.

Conclusions

Our data do not support an increased risk of earlier recurring moderate or severe relapses in patients hospitalised with eosinophilic exacerbations of COPD. Eosinophilic severe exacerbations present a variable phenotype.
Association between body mass index and mortality in hospitalised patients with community-acquired pneumonia
Authors: Kim Richard Y. , Glick Connor , Furmanek Stephen , Ramirez Julio A. , Cavallazzi Rodrigo
Published: January 2021

The obesity paradox postulates that increased body mass index (BMI) is protective in certain patient populations. We aimed to investigate the association of BMI and different weight classes with outcomes in hospitalised patients with community-acquired pneumonia (CAP).

This cohort study is a secondary data analysis of the University of Louisville Pneumonia Study database, a prospective study of hospitalised adult patients with CAP from June, 2014, to May, 2016, in Louisville, KY, USA. BMI as a predictor was assessed both as a continuous and categorical variable. Patients were categorised as weight classes based on World Health Organization definitions: BMI of <18.5 kg·m−2(underweight), BMI of 18.5 to <25 kg·m−2(normal weight), BMI of 25.0 to <30 kg·m−2(overweight), BMI of 30 to <35 kg·m−2(obesity class I), BMI of 35 to <40 kg·m−2(obesity class II), and BMI of ≥40 kg·m−2(obesity class III). Study outcomes, including time to clinical stability, length of stay, clinical failure and mortality, were assessed in hospital, at 30 days, at 6 months and at 1 year. Clinical failure was defined as the need for noninvasive ventilation, invasive ventilation or vasopressors within 1 week of admission. Patient characteristics and crude outcomes were stratified by BMI categories, and generalised additive binomial regression models were performed to analyse the impact of BMI as a continuous variable on study outcomes adjusting for possible confounding variables.

7449 patients were included in the study. Median time to clinical stability was 2 days for every BMI group. There was no association between BMI as a continuous predictor and length of stay <5 days (chi-squared=1.83, estimated degrees of freedom (EDF)=2.74, p=0.608). Clinical failure was highest in the class III obesity group, and higher BMI as a continuous predictor was associated with higher odds of clinical failure. BMI as a continuous predictor was significantly associated with 30-day (chi-squared=39.97, EDF=3.07, p<0.001), 6-month (chi-squared=89.42, EDF=3.44, p<0.001) and 1-year (chi-squared=83.97, EDF=2.89, p<0.001) mortalities. BMI ≤24.14 kg·m−2was a risk factor whereas BMI ≥26.97 kg·m−2was protective for mortality at 1-year. The incremental benefit of increasing BMI plateaued at 35 kg·m−2.

We found a protective benefit of obesity on mortality in CAP patients. However, we uniquely demonstrate that the association between BMI and mortality is not linear, and no incremental benefit of increasing BMI levels is observed in those with obesity classes II and III.
A toolkit for studying Varroa genomics and transcriptomics: preservation, extraction, and sequencing library preparation
Authors: Hasegawa Nonno , Techer Maeva , Mikheyev Alexander S.
Published: January 2021

Background

The honey bee parasite, Varroa destructor, is a leading cause of honey bee population declines. In addition to being an obligate ectoparasitic mite, Varroa carries several viruses that infect honey bees and act as the proximal cause of colony collapses. Nevertheless, until recently, studies of Varroa have been limited by the paucity of genomic tools. Lab- and field-based methods exploiting such methods are still nascent. This study developed a set of methods for preserving Varroa DNA and RNA from the field to the lab and processing them into sequencing libraries. We performed preservation experiments in which Varroa mites were immersed in TRIzol, RNAlater, and absolute ethanol for preservation periods up to 21 days post-treatment to assess DNA and RNA integrity.

Results

For both DNA and RNA, mites preserved in TRIzol and RNAlater at room temperature degraded within 10 days post-treatment. Mites preserved in ethanol at room temperature and 4 °C remained intact through 21 days. Varroa mite DNA and RNA libraries were created and sequenced for ethanol preserved samples, 15 and 21 days post-treatment. All DNA sequences mapped to the V. destructor genome at above 95% on average, while RNA sequences mapped to V. destructor, but also sometimes to high levels of the deformed-wing virus and to various organisms.

Conclusions

Ethanolic preservation of field-collected mites is inexpensive and simple, and allows them to be shipped and processed successfully in the lab for a wide variety of sequencing applications. It appears to preserve RNA from both Varroa and at least some of the viruses it vectors.
Comparison of hypoxemia, intubation procedure, and complications for non-invasive ventilation against high-flow nasal cannula oxygen therapy for patients with acute hypoxemic respiratory failure: a non-randomized retrospective analysis for effectiveness and safety (NIVaHIC-aHRF)
Authors: Zhang Chao , Ou Min
Published: January 2021

Background

Optimization of preoxygenation procedure can help to secure the method of intubation by reducing the risks of severe hypoxemia and other problems. There is confusion for efficacy of non-invasive ventilation compared to high-flow oxygen therapy regarding occurrence of severe hypoxemia during the intubation procedure. The purpose of the study was to compare the difference between noninvasive ventilation and high flow oxygen therapy to prevent desaturation during laryngoscopy.

Methods

Patients underwent high-flow nasal cannula oxygen therapy (HCO cohort, n = 161) or non-invasive ventilation procedure (NIV cohort, n = 154) for oxygenation and ventilation due to acute hypoxemic respiratory failure in the intensive care unit. Data before preoxygenation, preoxygenation, intubation, laryngoscopy, and complications of patients due to tracheal intubation were retrospectively collected and analyzed.

Results

There was no difference between both cohorts for the demographical and clinical conditions of the patients before preoxygenation (p > 0.05 for all parameters), numbers of patients with severe hypoxia during the intubation procedure (35 vs. 45, p = 0.303), the time duration of laryngoscopy (p = 0.847), number of laryngoscopies attempts (p = 0.804), and immediate and late complications during the intubation procedure. The values of pulse oximetry were reported higher for patients of NIV cohort than those of HCO cohort during preoxygenation. Fewer numbers of patients were reported with severe hypoxia among patients of the NIV cohort than those of the HCO cohort (24 vs., 40, p = 0.042) who have moderate-to-severe hypoxemia (partial pressure of arterial oxygen to fraction of inspired oxygen ratio ≤ 200 mmHg) before preoxygenation. The most common complications were hypertension, pulmonary aspiration, and increased 30-day mortality.

Conclusions

When compared, there was no difference between non-invasive ventilation technique and high-flow oxygen therapy to minimize severe hypoxia prior to laryngoscopy and endotracheal intubation in patients with acute respiratory failure.
Steps towards implementing evidence-based screening in family medicine in Ukraine: SWOT-analysis of an approach of multidimensional empowerment
Authors: Kolesnyk Pavlo , Frese Thomas , Vinker Shlomo , Shushman Ivanna , Zharkova Albina , Messaadi Nassir , Kolesnyk Andriy , Bayen Sabine
Published: January 2021

Background

The purpose of this study is to forward the implementation of an operational evidence-based state screening program of common diseases in Ukraine, where currently no state-based and evidence-based screening (EBS) exists. EBS should be performed by Family Doctors in a primary care setting and concern prevalent diseases in adults, such as: obesity (BMI), hypertension (BP measurement), diabetes (glycaemia), dyslipidemia (cholesterol/lipids), colon cancer (FOBT/colonoscopy), breast cancer (mammography), STIs (chlamydia, syphilis), HIV, HBV, HCV (i.e. serology or other rapid tests), HPV (swabs), cervical cancer (test Pap). depression (i.e., PHQ-9), and smoking (i.e., Fagerstrom).

Methods

Four needs-based research actions were led among citizens and healthcare professionals, based on multidimensional empowerment. Internal Strengths and Weaknesses of the ongoing implementation process were identified through these studies, whereas external Opportunities and Threats were determined by the present socio-cultural and political context. This SWOT analysis is likely to guide future state-based initiatives to accomplish EBS implementation in Ukraine.

Results

Internal Strengths are the bottom-up multidimensional empowerment approach, teaching of EBS and the development of an internet-based platform “Screening adviser” to assist shared decision making for person-centred EBS programs. Internal Weaknesses identified for the Family Doctors are a heterogeneous screening and the risk of decreasing motivation to screen. External Opportunities include the ongoing PHC reform, the existent WONCA and WHO support, and the existence of EBS programs in Europe. External Threats are the lack of national guidelines, not fully introduced gate keeping system, the vulnerable socio-economic situation, the war situation in the East of Ukraine and the Covid-19 pandemic.

Conclusions

We started EBS implementation through research actions, based on a multidimensional empowerment of citizens, HCP and in EBS pathways involved stakeholder teams, to foster a sustainable operational human resource to get involved in that new EBS pathway to implement. The presented SWOT-analysis of this ongoing implementation process allows to plan and optimize future steps towards a state based and supports EBS program in Ukraine.
Prognostic value of low microRNA-34a expression in human gastrointestinal cancer: a systematic review and meta-analysis
Authors: Chen Yan-Ling , Liu Xiao-Lin , Li Ling
Published: January 2021

Background

Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs).

Methods

All eligible studies were found by searching PubMed, Web of Science and EMBASE, and survival results were extracted. Then, the hazard ratio (HR) with the corresponding 95% confidence interval (CI) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratios (ORs) and 95% CIs.

Results

A total of 20 studies were included in this meta-analysis. For overall survival (OS), lower miR-34a expression could probably predict poorer outcome in GICs, with a pooled HR of 1.86 (95% CI: 1.52–2.28, P < 0.01). For disease-free survival (DFS), progression-free survival (PFS), and recurrence-free survival (RFS), lower miR-34a expression was related to worse DFS/PFS/RFS with a pooled HR of 1.86 (95% CI: 1.31–2.63, P  <  0.01). A significant relation of differentiation/TNM stage/lymphatic metastasis and the expression level of miR-34a was identified.

Conclusion

This meta-analysis revealed that lower miR-34a expression is significantly connected with worse OS and DFS/PFS/RFS in GIC patients. In addition, the miR-34a expression level is relatively lower in patients with lymph node metastasis than in patients without lymph node metastasis, and decreased miR-34a expression levels are linked to poor tumour differentiation and late TNM stage. MiR-34a may become a new factor for the prognosis prediction and progression of GICs.
Patients with low nicotinamide N-methyltransferase expression benefit significantly from bevacizumab treatment in ovarian cancer
Authors: Li Jun , Yue Huiran , Yu Hailin , Lu Xin , Xue Xiaohong
Published: January 2021

Background

The role of nicotinamide N-methyltransferase (NNMT) in ovarian cancer is still elusive. Our aim is to explore the expression of NNMT in ovarian cancer and to assess its association with patient prognosis and treatment response.

Methods

We first analyzed the differential expression of NNMT among fallopian tube epithelium, primary ovarian cancers, metastatic ovarian cancers, and recurrent ovarian cancers using Gene Expression Ominus (GEO) database (GSE10971, GSE30587, GSE44104 and TCGA datasets). Then, we assessed the association of NNMT expression with clinical and molecular parameters using CSIOVDB database and GSE28739 dataset. Next, we evaluate the association of NNMT expression with the prognosis of ovarian cancer patients in both GSE9891 dataset and TCGA dataset. Finally, GSE140082 dataset was used to explore the association of NNMT expression with bevacizumab response.

Results

NNMT expression was significantly elevated in lymphovascular space invasion (LVSI)-positive ovarian cancers compared with that in LVSI-negative ovarian cancers (TCGA dataset, P < 0.05), Moreover, increased expression of NNMT was associated with increased tumor stage, grade, and mesenchymal molecular subtype (CSIOVDB database). Survival analysis indicated that increased expression of NNMT was associated with a reduced OS in both GSE9891 dataset (HR: 2.28, 95%CI: 1.51–3.43, Log-rank P < 0.001) and TCGA dataset (HR: 1.55, 95%CI: 1.02–2.36, Log-rank P = 0.039). Multivariate analysis further confirmed the negative impact of NNMT expression on OS in ovarian cancer patients in those two datasets. Furthermore, the NNMT-related nomogram showed that NNMT shared a larger contribution to OS, compared with debulking status. More interestingly, bevacizumab conferred significant improvements in OS for patients with low NNMT expression (HR: 0.56, 95%CI: 0.31–0.99, Log-rank P = 0.049). In contrast, patients with high NNMT expression didn’t benefit from bevacizumab treatment significantly (HR: 0.85, 95%CI: 0.48–1.49, Log-rank P = 0.561). NNMT expression was positively correlated with the expression of genes, LDHA and PGAM1, involved in Warburg effect.

Conclusions

In conclusion, NNMT expression is associated with the aggressive behavior of ovarian cancer, correlates with a poor prognosis, and is predictive of sensitivity to bevacizumab treatment.
Detection of active and inactive phases of thyroid-associated ophthalmopathy using deep convolutional neural network
Authors: Lin Chenyi , Song Xuefei , Li Lunhao , Li Yinwei , Jiang Mengda , Sun Rou , Zhou Huifang , Fan Xianqun
Published: January 2021

Background

This study aimed to establish a deep learning system for detecting the active and inactive phases of thyroid-associated ophthalmopathy (TAO) using magnetic resonance imaging (MRI). This system could provide faster, more accurate, and more objective assessments across populations.

Methods

A total of 160 MRI images of patients with TAO, who visited the Ophthalmology Clinic of the Ninth People’s Hospital, were retrospectively obtained for this study. Of these, 80% were used for training and validation, and 20% were used for testing. The deep learning system, based on deep convolutional neural network, was established to distinguish patients with active phase from those with inactive phase. The accuracy, precision, sensitivity, specificity, F1 score and area under the receiver operating characteristic curve were analyzed. Besides, visualization method was applied to explain the operation of the networks.

Results

Network A inherited from Visual Geometry Group network. The accuracy, specificity and sensitivity were 0.863±0.055, 0.896±0.042 and 0.750±0.136 respectively. Due to the recurring phenomenon of vanishing gradient during the training process of network A, we added parts of Residual Neural Network to build network B. After modification, network B improved the sensitivity (0.821±0.021) while maintaining a good accuracy (0.855±0.018) and a good specificity (0.865±0.021).

Conclusions

The deep convolutional neural network could automatically detect the activity of TAO from MRI images with strong robustness, less subjective judgment, and less measurement error. This system could standardize the diagnostic process and speed up the treatment decision making for TAO.
Growth, puberty, and bone health in children and adolescents with inflammatory bowel disease
Authors: Jin Hye-Young , Lim Jae-Sang , Lee Yena , Choi Yunha , Oh Seak-Hee , Kim Kyung-Mo , Yoo Han-Wook , Choi Jin-Ho
Published: January 2021

Background

Endocrine complications such as impaired growth, delayed puberty, and low bone mineral density (BMD) can be associated with inflammatory bowel disease (IBD) in children and adolescents. This study was performed to investigate the frequency, characteristics, and outcomes of endocrine complications of IBD in children and adolescents.

Methods

This study included 127 patients with IBD diagnosed before 18 years of age [117 with Crohn disease (CD) and 10 with ulcerative colitis (UC)]. Growth profiles, pubertal status, 25-hydroxyvitamin D3[25(OH)D3] levels, and BMD were reviewed retrospectively.

Results

Short stature was observed in 14 of 127 (11.0 %) with a mean height-SDS of -2.31 ± 0.72. During a 2-year follow-up period, height-SDS did not significantly improve, while weight-SDS significantly improved. Among 109 patients who were older than 13 (girls) or 14 (boys) years of age during the study period, 11 patients (10.1 %) showed delayed puberty, which was associated with low weight-SDS. Vitamin D deficiency was documented in 81.7 % (94/115) with the average 25(OH)D3level of 14.5 ± 7.0 ng/mL. Lumbar BMD Z-score was below − 2 SDS in 25 of 119 patients (21.0 %). Height-SDS, weight-SDS, and body mass index (BMI)-SDS were lower in patients with osteoporosis than those without osteoporosis. When pediatric CD activity index scores were high (≥ 30), weight-SDS, BMI-SDS, insulin-like growth factor 1 (IGF-1)-SDS, and testosterone levels were significantly decreased.

Conclusions

Vitamin D deficiency and osteoporosis are common in pediatric IBD patients. As disease severity deteriorates, weight-SDS, IGF-1-SDS, and testosterone levels were decreased. Optimal pubertal development is necessary for bone health.
One year follow-up and mediation in cognitive behavioral therapy and acceptance and commitment therapy for adult depression
Authors: A-Tjak Jacqueline G. L. , Morina Nexhmedin , Topper Maurice , Emmelkamp Paul M. G.
Published: January 2021

Background

Existing therapies for depression are effective, but many patients fail to recover or relapse. To improve care for patients, more research into the effectiveness and working mechanisms of treatments is needed. We examined the long-term efficacy of Cognitive Behavioral Therapy (CBT) and Acceptance and Commitment Therapy (ACT) for Major Depressive Disorder (MDD), testing the hypothesis that CBT outperforms ACT and that both therapies work through their designated mechanisms of change.

Methods

We conducted a randomized controlled trial with 82 patients suffering from MDD. Data were collected before, during and after treatment, and at 12-month follow-up, assessing symptoms of depression, quality of life, dysfunctional attitudes, decentering, and experiential avoidance.

Results

Patients in both conditions reported significant and large reductions of depressive symptoms (d= − 1.26 to − 1.60) and improvement in quality of life (d= 0.91 to − 1.28) 12 months following treatment. Our findings indicated no significant differences between the two interventions. Dysfunctional attitudes and decentering mediated treatment effects of depressive symptoms in both CBT and ACT, whereas experiential avoidance mediated treatment effects in ACT only.

Conclusions

Our results indicate that CBT is not more effective in treating depression than ACT. Both treatments seem to work through changes in dysfunctional attitudes and decentering, even though the treatments differ substantially. Change in experiential avoidance as an underlying mechanism seems to be an ACT-specific process. Further research is needed to investigate whether ACT and CBT may work differently for different groups of patients with depression.

Trial registration

clinicaltrials.gov;NCT01517503. Registered 25 January 2012 - Retrospectively registered.
Relationship between the duration of smoking and blood pressure in Han and ethnic minority populations: a cross-sectional study in China
Authors: Zhang Yuelun , Feng Yunying , Chen Shi , Liang Siyu , Wang Shirui , Xu Ke , Ning Dongping , Yuan Xianxian , Zhu Huijuan , Pan Hui , Shan Guangliang
Published: January 2021

Background

Evidence for correlation between the cigarette use and blood pressure change remains ambiguous. This study modelled relationship between the duration of smoking and systolic blood pressure in a large national multi-ethnic cross-sectional survey in China.

Methods

Participants were selected through a multi-stage probability sampling procedure from 2012 to 2017. Former or current smokers were included in this study, whose smoking behaviour, blood pressure, and other demographic information were collected and measured through a face-to-face interview. Linear and non-linear relationships between the duration of smoking and systolic blood pressure were analysed and differences of the association between Han and minority populations were specially checked.

Results

A total of 8801 participants were enrolled in this study. Prevalence of hypertension was 41.3 and 77.8% were current smokers. For every additional year of smoking duration, systolic blood pressure raised by 0.325 mmHg (95% CI 0.296 to 0.354 mmHg, P <  0.001). The Chinese minority populations may suffer more from the elevated blood pressure in long-term smoking than Han populations (0.283 mmHg (95% CI 0.252 to 0.314 mmHg, P <  0.001) versus 0.450 mmHg (95% CI 0.380 to 0.520 mmHg, P <  0.001) raise in systolic blood pressure with each additional year of smoking in minority and Han populations).

Conclusions

Smoking is associated with raised systolic blood pressure in Chinese population. This association is notedly stronger in Chinese minority populations.
Short-term effectiveness of precise safety decompression via double percutaneous lumbar foraminoplasty and percutaneous endoscopic lumbar decompression for lateral lumbar spinal canal stenosis: a prospective cohort study
Authors: Wang Yu , Deng Mingyan , Wu Hao , Wu Ye , Guo Chuan , Zhang Dongfeng , Kong Qingquan
Published: January 2021

Purpose

This prospective cohort study reports on a modified technique, namely precise safety decompression via double percutaneous lumbar foraminoplasty (DPLF) and percutaneous endoscopic lumbar decompression (PELD) for lateral lumbar spinal canal (LLSC) stenosis, and its short-term clinical outcomes.

Methods

The study analyzed 69 patients with single-level LLSC stenosis simultaneously occurring in both zones 1 and 2 (defined as retrodiscal space and upper bony lateral recess respectively by new LLSC classification) who underwent DPLF–PELD from November 2018 to April 2019. Clinical outcomes were evaluated according to preoperative, 3 months postoperatively, and last follow-up, via leg pain/low back pain (LBP) visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, and the Macnab criteria. The postoperative MRI and CT were used to confirm the complete decompression, and flexion-extension x-rays at the last follow-up were used to observe lumbar stability.

Results

All patients successfully underwent DPLF–PELD, and the stenosis was completely decompressed, confirmed by postoperative MRI and CT. The mean follow-up duration was 13 months (range: 8–17 months). The mean preoperative leg pain VAS score is 7.05 ± 1.04 (range 5–9), which decreased to 1.03 ± 0.79(range: 0–3) at 3 months postoperatively and to 0.75 ± 0.63 (range: 0–2) by the last follow-up visit (p < 0.05). The mean preoperative ODI was 69.8 ± 9.05 (range: 52–85), which decreased to 20.3 ± 5.52 (range: 10–35) at the third month postoperatively and to 19.6 ± 5.21 (range: 10–34) by the final follow-up visit (p < 0.05). The satisfactory (excellent or good) results were 94.2%. There was one patient with aggravated symptoms, which were relieved after an open surgery. Two patients had a dural tear, and two patients suffered postoperative LBP. No recurrence or segmental instability was observed at the final follow-up.

Conclusion

DPLF–PELD could be a good alternative for the treatment of LLSC stenosis patients whose stenosis occurred in both zones 1 and 2.

Trial registration

Chinese Clinical Trial Registry (ChiCTR1800019551). Registered 18 November 2018.
Developing a family-reported measure of experiences with home-based pediatric palliative and hospice care: a multi-method, multi-stakeholder approach
Authors: Boyden Jackelyn Y. , Feudtner Chris , Deatrick Janet A. , Widger Kimberley , LaRagione Gwenn , Lord Blyth , Ersek Mary
Published: January 2021

Background

Many children with serious illnesses are receiving palliative and end-of-life care from pediatric palliative and hospice care teams at home (PPHC@Home). Despite the growth in PPHC@Home, no standardized measures exist to evaluate whether PPHC@Home provided in the U.S. meets the needs and priorities of children and their families.

Methods

We developed and conducted a preliminary evaluation of a family-reported measure of PPHC@Home experiences using a multi-method, multi-stakeholder approach. Our instrument development process consisted of four phases. Item identification and development (Phase 1) involved a comprehensive literature search of existing instruments, guidelines, standards of practice, and PPHC@Home outcome studies, as well as guidance from a PPHC stakeholder panel. Phase 2 involved the initial item prioiritization and reduction using a discrete choice experiment (DCE) with PPHC professionals and parent advocates. Phase 3 involved a second DCE with bereaved parents and parents currently receiving care for their child to further prioritize and winnow the items to a set of the most highly-valued items. Finally, we conducted cognitive interviews with parents to provide information about the content validity and clarity of the newly-developed instrument (Phase 4).

Results

Items were compiled predominantly from three existing instruments. Phase 2 participants included 34 PPHC providers, researchers, and parent advocates; Phase 3 participants included 47 parents; and Phase 4 participants included 11 parents. At the completion of Phase 4, the Experiences of Palliative and Hospice Care for Children and Caregivers at Home (EXPERIENCE@Home) Measure contains 22 of the most highly-valued items for evaluating PPHC@Home. These items include “The care team treats my child’s physical symptoms so that my child has as good a quality of life as possible”, “I have regular access to on-call services from our care team”, and “The nurses have the knowledge, skills, and experience to support my child’s palliative or hospice care at home.”

Conclusions

The EXPERIENCE@Home Measure is the first known to specifically measure family-reported experiences with PPHC@Home in the U.S. Future work will include formal psychometric evaluation with a larger sample of parents, as well as evaluation of the clinical utility of the instrument with PPHC@Home teams.
Honey and its nutritional and anti-inflammatory value
Authors: Ranneh Yazan , Akim Abdah Md , Hamid Hasiah Ab. , Khazaai Huzwah , Fadel Abdulmannan , Zakaria Zainul Amiruddin , Albujja Mohammed , Bakar Mohd Fadzelly Abu
Published: January 2021

Inflammation is the main key role in developing chronic diseases including cancer, cardiovascular diseases, diabetes, arthritis, and neurodegenerative diseases which possess a huge challenge for treatment. With massively compelling evidence of the role played by nutritional modulation in preventing inflammation-related diseases, there is a growing interest into the search for natural functional foods with therapeutic and preventive actions. Honey, a nutritional healthy product, is produced mainly by two types of bees: honeybee and stingless bee. Since both types of honey possess distinctive phenolic and flavonoid compounds, there is recently an intensive interest in their biological and clinical actions against inflammation-mediated chronic diseases. This review shed the light specifically on the bioavailability and bioaccessibility of honey polyphenols and highlight their roles in targeting inflammatory pathways in gastrointestinal tract disorders, edema, cancer, metabolic and cardiovascular diseases and gut microbiota.
Luteolin ameliorates lipopolysaccharide-induced microcirculatory disturbance through inhibiting leukocyte adhesion in rat mesenteric venules
Authors: Su Jie , Xu Han-Ting , Yu Jing-Jing , Yan Mei-Qiu , Wang Ting , Wu Ya-Jun , Li Bo , Lu Wen-Jie , Wang Chuan , Lei Shan-Shan , Chen Si-Min , Chen Su-Hong , Lv Gui-Yuan
Published: January 2021

Background

Microcirculatory disturbance is closely associated with multiple diseases such as ischemic and septic stroke. Luteolin (3,4,5,7-tetrahydroxyflavone) is a vascular protective flavonoid present in several dietary foods. However, how luteolin plays a role in microcirculatory disturbance is still unknown. The purpose of this study was to find out the influence of luteolin on the lipopolysaccharide (LPS)-induced microcirculatory disturbance, focusing on its effect on leukocyte adhesion and the underlying mechanism of this effect.

Methods

After injecting LPS into rats, we used an inverted intravital microscope to observe the velocity of red blood cells in venules, numbers of leukocytes adherent to and emigrated across the venular wall, hydrogen peroxide production in venular walls and mast cell degranulation. Intestinal microcirculation blood flow was measured by High-resolution Laser Doppler Perfusion Imaging. Histological changes of small intestine and mesenteric arteries were evaluated. Additionally, cell adhesion stimulated by LPS was tested on EA.hy926 and THP-1 cells. The production of pro-inflammatory cytokines, adhesion molecules and the activation of TLR4/Myd88/NF-κB signaling pathway were determined.

Results

The results showed luteolin significantly inhibited LPS-induced leukocyte adhesion, hydrogen peroxide production and mast cell degranulation, and increased intestinal microcirculation blood flow and ameliorated pathological changes in the mesenteric artery and the small intestine. Furthermore, luteolin inhibited the release of pro-inflammatory cytokines, the expression of TLR4, Myd88, ICAM-1, and VCAM-1, the phosphorylation of IκB-α and NF-κB/p65 in LPS stimulated EA.hy926.

Conclusions

Our findings revealed that it is likely that luteolin can ameliorate microcirculatory disturbance. The inhibitory effects of luteolin on the leukocyte adhesion stimulated by LPS, which participates in the development of microcirculatory disturbance, are mediated through the regulation of the TLR4/Myd88/NF-κB signaling pathway.
Polyphenolics and triterpenes presence in chloroform extract of Dicranopteris linearis leaves attenuated paracetamol-induced liver intoxication in rat
Authors: Zakaria Zainul Amiruddin , Sahmat Adibah , Azmi Azfar Hizami , Nur Zainol Amal Syahirah , Omar Maizatul Hasyima , Balan Tavamani , Sulistyorini Lilis , Azizah R. , Abdullah Muhammad Nazrul Hakim
Published: January 2021

Introduction

Water-soluble, but not lipid-soluble, extract of Dicranopteris linearis leaves has been proven to possess hepatoprotective activity. The present study aimed to validate the hepatoprotective and antioxidant activities, and phytoconstituents of lipid-soluble (chloroform) extract of D. linearis leaves.

Methods

The extract of D. linearis leaves (CEDL; 50, 250 and 500 mg/kg) was orally administered to rats for 7 consecutive days followed by the oral administration of 3 g/kg PCM to induce liver injury. Blood was collected for liver function analysis while the liver was obtained for histopathological examination and endogenous antioxidant activity determination. The extract was also subjected to antioxidant evaluation and phytochemicals determination via phytochemical screening, HPLC and UPLC-HRMS analyses.

Results

CEDL exerted significant (p < 0.05) hepatoprotective activity at 250 and 500 mg/kg and significantly (p < 0.05) reversed the PCM-induced decrease in rat’s liver endogenous antioxidant (catalase and superoxide dismutase) level. CEDL possessed a high antioxidant capacity when measured using the ORAC assay, but a low total phenolic content value and radical scavenging activity as confirmed via several radical scavenging assays, which might be attributed particularly to the presence of triterpenes. Phytochemicals screening demonstrated the presence of triterpenes and flavonoids, while UPLC-HRMS analysis showed the presence of polyphenols belonging to the hydroxybenzoic acids, hydroxycinammates and flavonoid groups.

Discussion and conclusion

Lipid-soluble bioactive compounds of CEDL demonstrated hepatoprotective effect against PCM intoxication partly via the modulation of the endogenous antioxidant defense system, and exerted high antioxidant capacity. Further investigation is warranted to identify the potential hepatoprotective leads from CEDL for future drug development.
Bushen Huoxue recipe attenuates early pregnancy loss via activating endometrial COX2-PGE2 angiogenic signaling in mice
Authors: Song Yufan , Zhou Fanru , Tan Xiujuan , Liu Xia , Ding Jiahui , Zhang Chu , Li Fan , Zhu Wenxin , Ma Wenwen , Hu Runan , Zhang Mingmin
Published: January 2021

Background

During the fresh cycles of in vitro fertilization and embryo transfer, a disturbance in the reproductive endocrine environment following controlled ovarian hyperstimulation (COH) is closely related to compromised endometrial receptivity. This is a major disadvantage for women during pregnancy. Based on the theory of traditional Chinese medicine, Bushen Huoxue recipe (BSHXR) has been indicated to facilitate embryo implantation.

Methods

The COH model (Kunming breed) was induced by injecting mice with pregnant mare serum gonadotrophin (0.4 IU/g) and human chorionic gonadotropin (1 IU/g), followed by treatment with BSHXR at three different concentrations (5.7, 11.4, and 22.8 g/kg), Bushen recipe (BSR) (5.7 g/kg), and Huoxue recipe (HXR) (5.7 g/kg). After successful mating, the pregnancy rate and implantation sites were examined on embryo day 8 (ED8), and the weight ratio of endometrium was calculated on ED4 midnight. Serum estrogen, progesterone, and endometrial PGE2 levels were measured using enzyme-linked immunosorbent assay. The endometrial microvasculature was evaluated using CD31 immunostaining. The protein and mRNA levels of the angiogenic factors in the endometrium were evaluated using western blot, immunohistochemistry, and polymerase chain reaction.

Results

In the COH group, the pregnancy rate and implantation sites were significantly decreased, and abnormal serum hormone levels and impaired endometrial vascular development were observed. After BSHXR treatment, the supraphysiological serum progesterone level in COH mice was restored to normalcy. Moreover, the abnormal expression of the endometrial pro-angiogenic factors, including HIF1α, COX2-PGE2 pathway, and the down-stream factors, namely, MMP2, MMP9, TIMP2, and FGF2 after subjecting mice to COH was significantly improved after BSHXR treatment.

Conclusion

BSHXR could improve embryo implantation by regulating hormonal balance and modulating endometrial angiogenesis in mice, without inducing any side effects in normal pregnancy.
Impact of career choice motivation on academic burnout in senior dental students: A cross-sectional study
Authors: Mohebbi Simin Z. , Gholami Mahdia , Chegini Mostafa , Ghoreyshi Younes , Gorter Ronald C. , Bahramian Hoda
Published: January 2021

Background

Motivation triggers all human activities including learning and lack of career motivation can lead to decreased efficiency. This study assessed the association between academic burnout and career choice motivation in senior dental students.

Methods

This cross-sectional study was performed on senior dental students of all four dental schools in Tehran in 2017. Dental students voluntarily filled out a 33-item questionnaire that comprised three sections. The first section included the Burnout Clinical Subtype Questionnaire (BCSQ-SS) with 12 questions addressing academic burnout. The second section consisted of 8 questions about career choice motivation, and the third section concentrated on 13 questions dealing with demographics. The individual scores of each section and the total scores were reported. The factor analysis of 8 questions about dental career choice motivation yielded 3 factors of social status and security, altruism, and others’ advice motivations. The data were analyzed using regression test.

Results

Totally, 131 students filled out the questionnaire (response rate = 86%). The total score of academic burnout was 38.89% ± 1.13%. The highest and the lowest burnout scores belonged to the domains of “overload” (46.69%± 1.46%) and “neglect” (31.98%± 1.32%), respectively. The most and the least frequently mentioned source of motivation for choosing dentistry were high income and failing to enter other fields, respectively. The burnout score was higher in students with altruism motivations (P = 0.007) and lower in students with others’ advice motivations (P = 0.004). The burnout score was higher in students with inadequate or moderate financial support from the family and lower in students whose mothers’ educational level was high-school diploma or lower.

Conclusion

Senior dental students in Tehran encountered different levels of academic burnout. In the present study, low financial support and altruism as career choice motivations were associated with higher level of academic burnout.
Verteporfin disrupts multiple steps of autophagy and regulates p53 to sensitize osteosarcoma cells
Authors: Saini Heena , Sharma Harshita , Mukherjee Sudeshna , Chowdhury Shibasish , Chowdhury Rajdeep
Published: January 2021

Background

Osteosarcoma (OS) is a malignant tumor of the bone mostly observed in children and adolescents. The current treatment approach includes neoadjuvant and adjuvant chemotherapy; however, drug resistance often hinders therapy in OS patients. Also, the post-relapse survival of OS patients is as low as 20%. We therefore planned to understand the molecular cause for its poor prognosis and design an appropriate therapeutic strategy to combat the disease.

Methods

We analyzed OS patient dataset from Gene Expression Omnibus (GEO) and identified the differentially expressed genes and the top deregulated pathways in OS. Subsequently, drugs targeting the major de-regulated pathways were selected and the following assays were conducted- MTT assay to assess cytotoxicity of drugs in OS cells; immunoblotting and immunostaining to analyze key protein expression and localization after drug treatment; LysoTracker staining to monitor lysosomes; Acridine Orange to label acidic vesicles; and DCFDA to measure Reactive Oxygen Species (ROS).

Results

The differential gene expression analysis from OS patient dataset implicated the striking involvement of cellular processes linked to autophagy and protein processing in the development of OS. We therefore selected the FDA approved drugs, chloroquine (CQ) and verteporfin (VP) known for autophagy inhibitory and proteotoxic functions to explore against OS. Importantly, VP, but not CQ, showed an extensive dose-dependent cytotoxicity. It resulted in autophagy disruption at multiple steps extending from perturbation of early autophagic processes, inhibition of autophagic flux to induction of lysosomal instability. Interestingly, VP treated protein lysates showed a ROS-dependent high molecular weight (HMW) band when probed for P62 and P53 protein. Further, VP triggered accumulation of ubiquitinated proteins as well. Since VP had a pronounced disruptive effect on cellular protein homeostasis, we explored the possibility of simultaneous inhibition of the ubiquitin-proteasomal system (UPS) by MG-132 (MG). Addition of a proteasomal inhibitor significantly aggravated VP induced cytotoxicity. MG co-treatment also led to selective targeting of P53 to the lysosomes.

Conclusion

Herein, we propose VP and MG induce regulation of autophagy and protein homeostasis which can be exploited as an effective therapeutic strategy against osteosarcoma.