bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum bilirubin level is associated with exercise capacity and quality of life in chronic obstructive pulmonary disease
Authors: Leem Ah Young , Kim Young Sam , Lee Ji-Hyun , Kim Tae-Hyung , Kim Ha Yan , Oh Yeon Mok , Lee Sang Do , Jung Ji Ye
Published: December 2019

Background

Bilirubin has antioxidant properties against chronic respiratory diseases. However, previous studies are limited by acquisition of serum bilirubin level at one time point and its analysis with clinical parameters. We evaluated the association of serum bilirubin levels with various clinical outcomes of chronic obstructive pulmonary disease (COPD) in Korean Obstructive Lung Disease (KOLD) cohort.

Methods

We included 535 patients with COPD from the KOLD cohort. Serum bilirubin levels and various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life (QoL), and exacerbation, were evaluated annually; their association was analyzed using generalized estimating equations and the linear mixed model.

Results

Among 535 patients, 345 (64.5%) and 190 (35.5%) were categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II and GOLD III-IV groups, respectively. 6 MW distance was positively associated with serum bilirubin levels, especially in the GOLD I-II group (estimated mean = 41.5). Among QoL indexes, the COPD assessment test score was negatively associated with serum bilirubin levels only in the GOLD I-II group (estimated mean = − 2.8). Higher serum bilirubin levels were independently associated with a higher number of acute exacerbation in the GOLD III-IV group (estimated mean = 0.45, P = 0.001). Multivariate analysis revealed that lung function and mortality were not associated with serum bilirubin levels.

Conclusions

Higher serum bilirubin levels were associated with a longer 6 MW distance and better QoL, especially in the GOLD I-II group, whereas they were related to a higher risk of acute exacerbation, especially in the GOLD III-IV group. Bilirubin levels may represent various conditions in COPD.
Longitudinal follow-up of health effects among workers handling engineered nanomaterials: a panel study
Authors: Wu Wei-Te , Li Lih-Ann , Tsou Tsui-Chun , Wang Shu-Li , Lee Hui-Ling , Shih Tung-Sheng , Liou Saou-Hsing
Published: December 2019

Background

Although no human illness to date is confirmed to be attributed to engineered nanoparticles, occupational epidemiological studies are needed to verify the health effects of nanoparticles. This study used a repeated measures design to explore the potential adverse health effects of workers handling nanomaterials.

Methods

Study population was 206 nanomaterial-handling workers and 108 unexposed controls, who were recruited from 14 nanotechnology plants. They were followed up no less than two times in four years. A questionnaire was used to collect potential confounders and detailed work conditions. Control banding was adopted to categorize risk level for each participant as a surrogate marker of exposure. Health hazard markers include cardiopulmonary dysfunction markers, inflammation and oxidative damage markers, antioxidant enzymes activity, and genotoxicity markers. The Generalized Estimating Equation model was applied to analyze repeated measurements.

Results

In comparison to the controls, a significant dose-dependent increase on risk levels for the change of superoxide dismutase (p<0.01) and a significant increase of glutathione peroxidase change in risk level 1 was found for nanomaterial-handling workers. However, the change of cardiovascular dysfunction, lung damages, inflammation, oxidative damages, neurobehavioral and genotoxic markers were not found to be significantly associated with nanomaterials handling in this panel study.

Conclusions

This repeated measurement study suggests that there was no evidence of potential adverse health effects under the existing workplace exposure levels among nanomaterials handling workers, except for the increase of antioxidant enzymes.
Fluoride exposure and sleep patterns among older adolescents in the United States: a cross-sectional study of NHANES 2015–2016
Authors: Malin Ashley J. , Bose Sonali , Busgang Stefanie A. , Gennings Chris , Thorpy Michael , Wright Robert O. , Wright Rosalind J. , Arora Manish
Published: December 2019

Background

Fluoride from environmental sources accumulates preferentially in the pineal gland which produces melatonin, the hormone that regulates the sleep-wake cycle. However, the effects of fluoride on sleep regulation remain unknown. This population-based study examined whether chronic low-level fluoride exposure is associated with sleep patterns and daytime sleepiness among older adolescents in the United States (US).

Method

This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2015–2016). We analyzed data from adolescents who had plasma fluoride (n = 473) and water fluoride (n = 419) measures and were not prescribed medication for sleep disorders. Relationships between fluoride exposure and self-reported sleep patterns or daytime sleepiness were examined using survey-weighted linear, binomial logistic or multinomial logistic regression after covariate adjustment. A Holm-Bonferroni correction accounted for multiple comparisons.

Results

The average age of adolescents was 17 years (range = 16–19). Median (IQR) water and plasma fluoride concentrations were 0.27 (0.52) mg/L and 0.29 (0.19) μmol/L respectively. An IQR increase in water fluoride was associated with 1.97 times higher odds of reporting symptoms suggestive of sleep apnea (95% CI: 1.27, 3.05; p = 0.02), a 24 min later bedtime (B = 0.40, 95% CI: 0.10, 0.70; p = 0.05), a 26 min later morning wake time (B = 0.43, 95% CI: 0.13, 0.73; p = 0.04), and among males, a 38% reduction in the odds of reporting snoring (95% CI: 0.45, 0.87, p = 0.03).

Conclusions

Fluoride exposure may contribute to changes in sleep cycle regulation and sleep behaviors among older adolescents in the US. Additional prospective studies are warranted to examine the effects of fluoride on sleep patterns and determine critical windows of vulnerability for potential effects.
Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells
Authors: Zhang Peng-Fei , Pei Xu , Li Ke-Sang , Jin Li-Na , Wang Fei , Wu Jing , Zhang Xue-Mei
Published: December 2019

Background

Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment.

Methods

The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p.

Results

Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy.

Conclusion

Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.
Employment preferences of obstetricians and gynecologists to work in the district hospitals: evidence from a discrete choice experiment in Nepal
Authors: Gautam Bishnu , Sapkota Vishnu Prasad , Wagle Rajendra Raj
Published: December 2019

Background

A mismatch between the requirement and annual production of obstetricians and gynecologists (OBs-GYNs) was observed in Nepal. On top of that, recruitment and retention of OBs-GYNs is a pressing problem, especially in district hospitals of Nepal. In this connection, evidence on the job priorities and preferences of OBs-GYNs, which is currently lacking in Nepal, would help in policymakers in devising recruitment and retention strategies in these hospitals. This study, therefore, aims at exploring the most relevant job attributes that OBs-GYNs would prefer to work in the district hospitals of Nepal using a discrete choice experiment (DCE) technique.

Methods

Job attributes relevant to design the questionnaire were identified using keyinformant interviews and focusgroup discussions with policymakers and top managers. Then, 48 choice sets were developed using a fractional factorial design. Using these unlabeled choice sets, a DCE was conducted among 189 OBs-GYNs. The multinomial logistic regression model was used to estimate the marginal utilities and other model parameters. The willingness to pay/accept estimates was also measured for each job attribute.

Results

OBs-GYNs preferred the presence of a full team at the workplace (OB-GYN, pediatrician, and anesthesiologist), provision of primary and secondary education for children, and opportunity of private practice. On the other hand, a few job attributes such as a higher duration of service in district hospitalsand the provisions of a car allowance were preferred less by the respondents. Results from the marginal utility by the OBs-GYNs would be open to trade among the attributes.

Conclusions

The job attributes identified as incentives in this study should be included in a package to attract OBs-GYNs to serve in district hospitals of Nepal rather than offering a standard incentive package to all health workers. Similarly, this study confirmed the importance of the combination of non-monetary and monetary interventions in attracting and retaining health workers in district hospitals of Nepal.
Accelerometry-assessed physical activity and sedentary time and associations with chronic disease and hospital visits - a prospective cohort study with 15 years follow-up
Authors: Dohrn Ing-Mari , Welmer Anna-Karin , Hagströmer Maria
Published: December 2019

Background

Associations of objectively assessed physical activity in different intensities and risk of developing chronic disease that requires hospital care have not yet been examined in long term population-based studies. Studies addressing the link between physical activity and sedentary time and subsequent hospital admissions are lacking.

Objective

To examine the prospective associations between physical activity and sedentary time with morbidity defined as: 1) a registered main diagnosis of cardiovascular disease, cancer, type-2 diabetes, dementia, obesity or depression; 2) number of in- and outpatient hospital visits; and 3) number of in-hospital days.

Methods

In total, 1220 women and men, 18–75 years, from the population-based Sweden Attitude Behaviour and Change study 2000–2001 were included. Time spent sedentary, in light-intensity physical activity and in moderate-to-vigorous physical activity, and total accelerometer counts were assessed using the ActiGraph 7164 accelerometer. Morbidity data were obtained 2016 from Swedish registers. Cox proportional hazards models estimated hazard ratios (HR) of morbidity with 95% confidence intervals (CI) and negative binomial regression estimated incidence rate ratio (IRR) with 95% CI for number of hospital visits, and length of hospital stay.

Results

Over a follow-up of 14.4 years (SD = 1.6), 342 persons had at least one registered hospital visit due to any of the included diagnoses. Higher moderate-to-vigorous physical activity was associated with significant risk reductions for combined morbidity (all included diagnoses) (HR: 0.65, 95% CI: 0.48–0.88) and cardiovascular disease (HR: 0.52, 95% CI: 0.33–0.82). Higher total counts showed similar results, and was also associated with fewer hospital visits (IRR = 0.56, 95% CI: 0.37–0.85). Higher sedentary time increased the risk of in-hospital days. (IRR = 2.38, 95% CI: 1.20–4.74).

Conclusion

This study supports the importance of moderate-to-vigorous physical activity for preventing chronic disease that requires hospital care, especially cardiovascular disease. High volumes of sedentary behavior may increase the risk of future hospitalization. Our results support the public health message “sit less and move more”.
Correlates of English local government use of the planning system to regulate hot food takeaway outlets: a cross-sectional analysis
Authors: Keeble Matthew , Adams Jean , White Martin , Summerbell Carolyn , Cummins Steven , Burgoine Thomas
Published: December 2019

Background

Greater neighbourhood takeaway food outlet access has been associated with increased takeaway food consumption and higher body weight. National planning guidelines in England suggest that urban planning could promote healthier food environments through takeaway food outlet regulation, for example by restricting the proliferation of outlets near schools. It is unknown how geographically widespread this approach is, or local characteristics associated with its use. We aimed to address these knowledge gaps.

Methods

We used data from a complete review of planning policy documents adopted by local government areas in England (n = 325), which contained policies for the purpose of takeaway food outlet regulation. This review classified local government area planning policies as having a health (diet or obesity) or non-health focus. We explored geographical clustering of similar planning policies using spatial statistics. We used multinomial logistic regression models to investigate whether the odds of planning policy adoption varied according to local characteristics, for example the proportion of children with excess weight or the current number of takeaway food outlets.

Results

We observed clusters of local government areas with similar adopted planning policies in the North East, North West, and Greater London regions of England. In unadjusted logistic regression models, compared to local government areas with the lowest, those with highest proportion of 10–11 year olds with excess weight (OR: 25.31; 95% CI: 6.74, 94.96), and takeaway food outlet number (OR: 54.00; 95% CI: 6.17, 472.41), were more likely to have a health-focused planning policy, than none. In models adjusted for deprivation, relationships for excess weight metrics were attenuated. Compared to local government areas with the lowest, those with the highest takeaway food outlet number remained more likely to have a health-focused planning policy, than none (OR: 16.98; 95% CI: 1.44, 199.04). When local government areas were under Labour political control, predominantly urban, and when they had more geographically proximal and statistically similar areas in the same planning policy status category, they were also more likely to have health-focused planning policies.

Conclusions

Planning policies for the purpose of takeaway food outlet regulation with a health focus were more likely in areas with greater numbers of takeaway food outlets and higher proportions of children with excess weight. Other characteristics including Labour political control, greater deprivation and urbanisation, were associated with planning policy adoption, as were the actions of similar and nearby local government areas. Further research should engage with local policymakers to explore the drivers underpinning use of this approach.
Prognostic nomogram for bladder cancer with brain metastases: a National Cancer Database analysis
Authors: Yao Zhixian , Zheng Zhong , Ke Wu , Wang Renjie , Mu Xingyu , Sun Feng , Wang Xiang , Garg Shivank , Shi Wenyin , He Yinyan , Liu Zhihong
Published: December 2019

Background

This study aimed to establish and validate a nomogram for predicting brain metastasis in patients with bladder cancer (BCa) and assess various treatment modalities using a primary cohort comprising 234 patients with clinicopathologically-confirmed BCa from 2004 to 2015 in the National Cancer Database.

Methods

Machine learning method and Cox model were used for nomogram construction. For BCa patients with brain metastasis, surgery of the primary site, chemotherapy, radiation therapy, palliative care, brain confinement of metastatic sites, and the Charlson/Deyo Score were predictive features identified for building the nomogram.

Results

For the original 169 patients considered in the model, the areas under the receiver operating characteristic curve (AUC) were 0.823 (95% CI 0.758–0.889, P < 0.001) and 0.854 (95% CI 0.785–0.924, P < 0.001) for 0.5- and 1-year overall survival respectively. In the validation cohort, the nomogram displayed similar AUCs of 0.838 (95% CI 0.738–0.937, P < 0.001) and 0.809 (95% CI 0.680–0.939, P < 0.001), respectively. The high and low risk groups had median survivals of 1.91 and 5.09 months for the training cohort and 1.68 and 8.05 months for the validation set, respectively (both P < 0.0001).

Conclusions

Our prognostic nomogram provides a useful tool for overall survival prediction as well as assessing the risk and optimal treatment for BCa patients with brain metastasis.
Idiopathic mast cell activation syndrome and radiation therapy: a case study, literature review, and discussion of mast cell disorders and radiotherapy
Authors: Landy Robin E. , Stross William C. , May Jackson M. , Kaleem Tasneem A. , Malouff Timothy D. , Waddle Mark R. , Vallow Laura A.
Published: December 2019

Background

Mast Cell Activation Syndrome (MCAS) is classified as an idiopathic mast cell disorder where inconsistent or unknown triggers release inflammatory mediators and cause a constellation of symptoms. Studies demonstrate mast cells increase histamine, tryptase, and inflammatory cytokine expression following ionizing radiation. Additionally, there are cases of cutaneous mastocytosis developing within the initial radiation field suggesting mast cells play a role in local tissue reactions. Literature is sparse on radiation induced toxicity in patients with mast cell disorders.

Case presentation

A 62 year old female patient with a history of MCAS received breast conservation therapy for invasive lobular carcinoma of the left breast initially AJCC 7th Stage IIB, pT3 pN0 M0. The patient underwent external beam radiotherapy (EBRT) and received 4500 cGy to the left whole breast, followed by a 1000 cGy boost to the lumpectomy cavity. She developed grade 1 radiation dermatitis. Two years later she progressed distantly and received stereotactic body radiation therapy to a lumbar vertebrae lesion to a dose of 2400 cGy in a single fraction. She developed no in-field dermatologic or systemic flare in her MCAS symptoms during radiation therapy.

Conclusions

To our knowledge there are no reported cases in the literature of patients diagnosed with MCAS or other idiopathic mast cell disorders undergoing radiation therapy. Idiopathic mast cell disorders such as MCAS and primary mast cell disorders alike should not be considered a contraindication to treatment with EBRT. This patient population appears to tolerate treatment without systemic flares in symptoms.
Effect of altered proximal femoral geometry on predicting femoral stem anteversion in patients with developmental dysplasia of the hip
Authors: Huang Chenhui , Tan Haitao , Kernkamp Willem Alexander , Cheng Rongshan , Liang Junjie , Zhu Zhenan , Baek Seung-Hoon , Wang Liao , Tsai Tsung-Yuan
Published: December 2019

Background

The deformity of the proximal femur and acetabular in patients with developmental dysplasia of the hip (DDH) renders an intraoperative decision for ideal component placement challenging. We hypothesized that the altered morphology of calcar femorale (CF) in DDH patients changed the fixation mechanism of the cementless metaphyseal-filling stem and aimed to predict stem anteversion using proximal femoral anatomical parameters from preoperative CT.

Methods

Preoperative and postoperative CT scans of 34 DDHs with a metaphyseal-filling stem in THA were retrospectively analyzed. Proximal femoral anatomical parameters, including the femoral anteversion (FA) and the CF angles at the low femoral neck (LFN) and the center of the lesser trochanter (CLT) levels (FA-LFN, FA-CLT, CF-LFN, and CF-CLT) were measured. The dysplastic hips were divided into the CF group (n = 21) and the non-CF group (n = 13) according to the presence of the CF-LFN. The association between the anatomical parameters and the postoperative stem anteversion was statistically analyzed, and the predicted stem anteversion was compared with postoperative stem anteversion.

Results

In the CF group, the combination of the CF-LFN and FA-CLT exhibited a strong positive correlation (R = 0.870, p < 0.001) with the postoperative stem anteversion. In the non-CF group, only the FA-LFN had a strong positive correlation (R = 0.864, p < 0.001). Average prediction errors were 5.9° and 6.4° in the CF and non-CF groups.

Conclusions

The presence of CF-LFN is related to the press-fit mechanism of the metaphyseal-filling stem, and the preoperative measurements from CT images can be employed as a tool to predict postoperative stem anteversion in DDH patients.
Topical application of Chinese herbal medicine DAEP relieves the osteoarthritic knee pain in rats
Authors: Siu Wing Sum , Shum Wai Ting , Cheng Wen , Wong Chun Wai , Shiu Hoi Ting , Ko Chun Hay , Leung Ping Chung , Lam Christopher Wai Kei , Wong Chun Kwok
Published: December 2019

Background

The potential adverse effects of conventional oral pharmacotherapy of osteoarthritis (OA) restrict their long-term use. Topical application of a Chinese herbal paste for relieving OA knee pain can be effective and safe. However, evidence-based scientific research is insufficient to support its application worldwide. The aim of this study was to investigate the in vivo efficacy of a topical Chinese herbal paste on relieving OA knee pain and its underlying mechanism.

Methods

An OA rat model was developed by anterior cruciate ligament transection (ACLT) followed by treadmill running. A herbal paste including Dipsaci Radix, Achyranthis Bidentatae Radix, Eucommiae Cortex and Psoraleae Fructus, named as DAEP, was applied topically on the knee joint of the rats (DAEP). The rats without DAEP treatment served as Control. Rats with surgery but without ACLT, treadmill running and DAEP treatment acted as Sham. The morphologic change of the knee joint was observed radiographically. Nociception from the knee of the rats was assessed using Incapacitent test and CatWalk gait system. The therapeutic mechanism was investigated by analyzing the gene and protein expression of inflammatory markers via qPCR and Western blot, respectively.

Results

Radiographic images showed less destruction at the posterior tibial plateau of the DAEP group compared with the Control after 2 weeks of treatment. The static weight ratio and the gait parameters of the Control were reduced significantly via Incapacitance test and CatWalk gait analysis, respectively. DAEP treatment increased the Print Area and Maximum Intensity significantly compared with the Control. DAEP significantly suppressed the upregulation of gene expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS).

Conclusions

DAEP exhibited its effect via the nuclear factor (NF)-κB pathway by suppressing the phosphorylation of IκB kinase αβ (p-IKKαβ) and cyclooxygenase-2 (COX-2) protein expression. This study provides scientific evidence to support the clinical application of the Chinese herbal paste on reliving OA pain.
Prenatal diagnosis of cri-du-chat syndrome by SNP array: report of twelve cases and review of the literature
Authors: Su Jiasun , Fu Huayu , Xie Bobo , Lu Weiliang , Li Wei , Wei Yuan , Zhang Qiang , Wei Shengkai , Chen Qiuli , Lu Yingchi , Jiang Tingting , Luo Jingsi , Qin Zailong
Published: December 2019

Background

Cri-du-chat syndrome (CdCS; OMIM#123450) is a classic contiguous gene syndrome caused by chromosome 5p terminal deletion (5p-), which characterized by a high-pitched cat-like cry, developmental delay, severe psychomotor, mental retardation, and dysmorphic features in infancy. Prenatal diagnosis of CdCS is difficult due to the non-specific ultrasound features. And reports using array analysis are rare. This study presented the first retrospective analysis of prenatal series of CdCS fetuses diagnosed by single nucleotide polymorphism (SNP) array in China.

Case presentation

A total of 35,233 pregnant women were enrolled from Jan 2014 to April 2019 in our center, there are twelve 5p- cases with abnormal sonographic signs revealed by SNP array, giving an incidence of 0.034% (12/35,233). Clinical information and molecular basis included: maternal demographics, indications for invasive testing, sonographic findings and SNP array results. Among all the 5p- cases revealed, nine cases were diagnosed by both karyotyping and SNP array, three cases were detected only by SNP array. Half of our cases (6/12) had an isolated 5p terminal deletion, which sizes ranged from 9.0 Mb to 30 Mb. The other half of cases (6/12) characterized by unbalanced translocation, with sex ratio 7:5 (female: male), when combine the clinical features observed from this study and available literature, the most frequent anomaly observed in prenatal ultrasound examination of CdCS was cerebral abnormalities, accounted for 44.4% (16/36) of the existing cases. Features that are less consistent included: choroid plexus cyst (13.8%, 5/36), single umbilical artery (13.3%, 4/30), ventricular septal defect (11.1%, 4/36), hydrops fetalis (8.3%, 3/36), ascites (8.3%, 3/36), increased NT/NF (8.3%, 3/36), absent/severely hypoplastic nasal bone (5.5%, 2/36), in order.

Conclusion

Prenatal findings such as cerebral abnormalities, absent/hypoplastic nasal bone, hydrops fetalis, ascites or encephalocele may act as suggestive signs of CdCS or other microdeletion/duplication syndromes. Combining typical karyotyping with chromosomal microarray analysis (CMA) is a definitive method for a precise diagnosis of CdCS and provides more accurate results in order to offer genetic counseling to families which need to deal with cryptic aberrations.
Zinc transporters in Alzheimer’s disease
Authors: Xu Yingshuo , Xiao Guiran , Liu Li , Lang Minglin
Published: December 2019

Alzheimer’s disease (AD) is the most devastating neurodegenerative disorder. Due to the increase in population and longevity, incidence will triple by the middle of the twenty-first century. So far, no treatment has prevented or reversed the disease. More than 20 years of multidisciplinary studies have shown that brain zinc dyshomeostasis may play a critical role in AD progression, which provides encouraging clues for metal-targeted therapies in the treatment of AD. Unfortunately, the pilot clinical application of zinc chelator and/or ionophore strategy, such as the use of quinoline-based compounds, namely clioquinol and PBT2, has not yet been successful. The emerging findings revealed a list of key zinc transporters whose mRNA or protein levels were abnormally altered at different stages of AD brains. Furthermore, specifically modulating the expression of some of the zinc transporters in the central nervous system through genetic methods slowed down or prevented AD progression in animal models, resulting in significantly improved cognitive performance, movement, and prolonged lifespan. Although the underlying molecular mechanisms are not yet fully understood, it shed new light on the treatment or prevention of the disease. This review considers recent advances regarding AD, zinc and zinc transporters, recapitulating their relationships in extending our current understanding of the disease amelioration effects of zinc transport proteins as potential therapeutic targets to cure AD, and it may also provide new insights to identify novel therapeutic strategies for ageing and other neurodegenerative diseases, such as Huntington’s and Parkinson’s disease.
Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer
Authors: Wang Hongbo , Lu Zaiming , Zhao Xiangxuan
Published: December 2019

Hepatocellular carcinoma (HCC, also called primary liver cancer) is one of the most fatal cancers in the world. Due to the insidiousness of the onset of HCC and the lack of effective treatment methods, the prognosis of HCC is extremely poor, and the 5-year average survival rate is less than 10%. Exosomes are nano-sized microvesicle and contain various components such as nucleic acids, proteins, and lipids. Exosomes are important carriers for signal transmission or transportation of material from cell to cell or between cells and tissues. In recent years, exosomes have been considered as potential therapeutic targets of HCC. A large number of reports indicate that exosomes play a key role in the establishment of an HCC microenvironment, as well as the development, progression, invasion, metastasis, and even the diagnosis, treatment, and prognosis of HCC. However, the exact molecular mechanisms and roles of exosomes in these processes remain unclear. We believe that elucidation of the regulatory mechanism of HCC-related exosomes and its signaling pathway and analysis of its clinical applications in the diagnosis and treatment of HCC can provide useful clues for future treatment regimens for HCC. This article discusses and summarizes the research progress of HCC-related exosomes and their potential clinical applications.
RETRACTED ARTICLE: m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis
Authors: Jin Dan , Guo Jiwei , Wu Yan , Du Jing , Yang Lijuan , Wang Xiaohong , Di Weihua , Hu Baoguang , An Jiajia , Kong Lingqun , Pan Lei , Su Guoming
Published: December 2019

Background

METTL3 is an RNA methyltransferase that mediates m6A modification and is implicated in mRNA biogenesis, decay, and translation. However, the biomechanism through which METTL3 regulates MALAT1-miR-1914-3p-YAP axis activity to induce NSCLC drug resistance and metastasis is not very clear.

Methods

The expression of mRNA was analyzed by qPCR assays. Protein levels were analyzed by western blotting and immunofluorescent staining. Cellular proliferation was detected by CCK8 assays. Cell migration and invasion were analyzed by wound healing and transwell assays, respectively. Promoter activities and gene transcription were analyzed by luciferase reporter assays. Finally, m6A modification was analyzed by MeRIP.

Results

METTL3 increased the m6A modification of YAP. METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. Moreover, the RNA level of MALAT1 was increased due to a higher level of m6A modification mediated by METTL3. Meanwhile, the stability of MALAT1 was increased by METTL3/YTHDF3 complex. Additionally, MALAT1 functions as a competing endogenous RNA that sponges miR-1914-3p to promote the invasion and metastasis of NSCLC via YAP. Furthermore, the reduction of YAP m6A modification by METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.

Conclusion

Results indicated that the m6A mRNA methylation initiated by METTL3 promotes YAP mRNA translation via recruiting YTHDF1/3 and eIF3b to the translation initiation complex and increases YAP mRNA stability through regulating the MALAT1-miR-1914-3p-YAP axis. The increased YAP expression and activity induce NSCLC drug resistance and metastasis.
miR-552 promotes ovarian cancer progression by regulating PTEN pathway
Authors: Zhao Wenman , Han Tao , Li Bao , Ma Qianyun , Yang Pinghua , Li Hengyu
Published: December 2019

Background

Increasing researches have demonstrated the critical functions of MicroRNAs (miRNAs) in the progression of malignant tumors, including ovarian cancer. It was reported that miR-552 was an important oncogene in both breast cancer and colorectal cancer. However, the role of miR-552 in ovarian cancer (OC) remains to be elucidated.

Methods

RT-PCR and western blot analysis were used to detect the expression of miR-552 and PTEN. The impact of miR-552 on ovarian cancer proliferation and metastasis was investigated in vitro. The prognostic value of miR-552 was evaluated using the online bioinformatics tool Kaplan-Meier plotter.

Results

In the present study, we for first found that miR-552 was upregulated in ovarian cancer, especially in metastatic and recurrence ovarian cancer. Forced miR-552 expression promotes the growth and metastasis of ovarian cancer cells. Consistently, miR-552 interference inhibits the proliferation and metastasis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified Phosphatase and tension homolog (PTEN) as a direct target of miR-552. miR-552 downregulated the PTEN mRNA and protein expression in ovarian cancer cells. Furthermore, the PTEN siRNA abolishes the discrepancy of growth and metastasis capacity between miR-552 mimic ovarian cells and control cells. More importantly, upregulation of miR-552 predicts the poor prognosis of ovarian cancer patients.

Conclusion

Our findings revealed that miR-552 could promote ovarian cancer cells progression by targeting PTEN signaling and might therefore be useful to predict patient prognosis.
Effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory biomarkers, tumor marker CEA, and nutritional status in patients with colorectal cancer: a study protocol for a double blind randomized controlled trial
Authors: Haidari Fatemeh , Abiri Behnaz , Iravani Masood , Razavi Seyed-Mohsen , Sarbakhsh Parvin , Ahmadi-Angali Kambiz , Vafa Mohammadreza
Published: December 2019

Background

Much evidence is available demonstrating that both vitamin D and omega-3 fatty acids block the development and progression of colonic carcinogenesis. The results of animal studies have shown that the consumption of omega-3 fatty acids can decrease inflammatory biomarkers, enhance the efficacy of chemotherapy, and decrease the side effects of chemotherapy or cancer. Also, observational studies propose that higher levels of 25(OH)D are related to improved survival of colorectal cancer patients. This study will aim to evaluate the effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory biomarkers, tumor marker CEA, and nutritional status in colorectal cancer patients.

Methods/design

We will carry out an 8-week double-blind randomized, placebo-controlled clinical trial to evaluate the effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory biomarkers, tumor marker CEA, and nutritional status in patients with stage ӀӀ or ӀӀӀ colorectal cancer undergoing chemotherapy.

Discussion

Because of the important effects of vitamin D and omega-3 fatty acids on molecular pathways involved in cancer development and progression, it seems that both vitamin D and omega-3 fatty acids may provide a new adjuvant therapy by decreasing inflammatory biomarkers and resistance to cancer treatment in patients with colorectal cancer.

Trial registration

Iranian Registry of Clinical TrialsIRCT20180306038979N1. Registered on 16 March 2018.
A pragmatic pilot phase II randomised controlled trial of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) in adult patients who are undergoing heart surgery (PROPHESY)
Authors: Green Laura , Roberts Neil , Cooper Jackie , Field Jane , Gill Ravi , Klein Andrew , Agarwal Seema , Stanworth Simon , Johnston Atholl , Monk Vivienne , O’Brien Ben
Published: December 2019

Background

Fresh frozen plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during or immediately after cardiac surgery. In the United Kingdom prothrombin complex concentrate (PCC) is not licensed in this setting, although it is being used in Europe because it has a higher concentration of clotting factor levels, and it can be administered rapidly and in small volume, resulting in less volume overload during cardiac surgery.

Methods

PROPHESY is a pragmatic, single-centre, open-label, randomised, controlled pilot trial that will assess whether it is feasible to perform a large trial in the future that will compare PCC versus FFP in patients who are bleeding (not on warfarin) and who require blood transfusion. Over a 15-month period, 50 patients will be randomised to PCC versus FFP if they develop active bleeding within 24 h of cardiac surgery and for whom the clinician has decided to administer FFP for treatment of bleeding. Standard laboratory and point-of-care assessments will be performed as per routine practice, and additional research blood samples will be taken at three time points to assess haemostasis. Subjects will be assessed daily up to hospital discharge or 30 days or death (whichever occurs first) and will be seen in follow-up for 90 days after surgery to assess for thromboembolic complications and hospital re-admission since discharge. Quality-of-life assessment will be performed pre-surgery and at 90 days post-surgery. We will also perform qualitative research with clinical experts and patients to explore the understanding of and experience with the interventions, as well as adherence to study procedures and protocol.

Discussion

There have been no randomised controlled trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery patients who are bleeding. This pilot study will assess if individual components of a large trial are deliverable to assess the safety and efficacy of the two blood products in the future.

Trial registration

EudraCT, 2018-003041-41; ClinicalTrials.gov, NCT03715348. Registered on 29 July 2018.
The effect of antibiotics on post-adenotonsillectomy morbidity in Tanzanian children: study protocol for a randomized, double-blind, placebo-controlled trial
Authors: Katundu Denis R. , Shija Peter S. , Nyombi Baltazari , Semvua Hadija , Oussoren Fieke K. , van Heerbeek Niels
Published: December 2019

Background

Adenotonsillectomy is the most frequently performed operation in children worldwide. For decades, prophylactic antibiotics have been prescribed to limit postoperative complications. The effect of this antibiotic use has been refuted in a Cochrane Review. However, all reviewed studies were carried out in developed countries. In Tanzania, like many other developing countries with limited resources and a high burden of infectious diseases, postoperative antibiotic prescription is still very common to decrease the supposed higher postoperative morbidity. However, as a consequence of this widespread use of postoperative antibiotics, cross-resistance and risk of allergic side effects rise. Well-designed randomized controlled trials are needed to limit unnecessary antibiotic prescription and secondary antibiotic resistance.

Aim

The aim of this study is to analyse the prophylactic role of postoperative antibiotics on morbidity following adenotonsillectomy in children in Tanzania.

Design

The double-blinded, randomized, placebo-controlled trial was set in northern Tanzania. Participating centres are the Department of Otolaryngology at Kilimanjaro Christian Medical Centre in Moshi and the Department of Paediatric Surgery at the Arusha Lutheran Medical Centre in Arusha.

Methods

Around 270 children aged 2–14 years, all scheduled for elective (adeno)tonsillectomy, will be included and assigned to receive either a standard regimen of 5 days of antibiotic prophylaxis or placebo after surgery. The primary outcomes are postoperative haemorrhage, fever and pain. Secondary outcomes are the time until normal diet is resumed, the time until normal activities are resumed and the occurrence of adverse events and microbial recolonization of the tonsillar beds.

Discussion

This study will enhance an increase of proper antimicrobial prescription in Tanzanian institutions as well as other resource-limited countries where prescription of antibiotics is still very common. In addition, it might augment current knowledge about surface and core tonsillar micro-organisms and sensitivity patterns.

Trial registration

Pan African Clinical Trials Registry, PACTR201905466349317. Retrospectively registered on 15 May 2019. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=8119
Principles and procedures for data and safety monitoring in pragmatic clinical trials
Authors: Simon Gregory E. , Shortreed Susan M. , Rossom Rebecca C. , Penfold Robert B. , Sperl-Hillen Jo Ann M. , O’Connor Patrick
Published: December 2019

Background

All clinical trial investigators have ethical and regulatory obligations to monitor participant safety and trial integrity. Specific procedures for meeting these obligations, however, may differ substantially between pragmatic trials and traditional explanatory clinical trials.

Methods/Results

Appropriate monitoring of clinical trials typically includes assessing rate of recruitment or enrollment; monitoring safe and effective delivery of study treatments; assuring that study staff act to minimize risks; monitoring quality and timeliness of study data; and considering interim analyses for early detection of benefit, harm, or futility. Each of these responsibilities applies to pragmatic clinical trials. Just as design of pragmatic trials typically involves specific and necessary departures from methods of explanatory clinical trials, appropriate monitoring of pragmatic trials typically requires specific departures from monitoring procedures used in explanatory clinical trials. We discuss how specific aspects of pragmatic trial design and operations influence selection of monitoring procedures and illustrate those choices using examples from three ongoing pragmatic trials conducted by the Mental Health Research Network.

Conclusions

Pragmatic trial investigators should not routinely adopt monitoring procedures used in explanatory clinical trials. Instead, investigators should consider core principles of trial monitoring and design monitoring procedures appropriate for each pragmatic trial.
Association of age, sex and BMI with the rate of change in tibial cartilage volume: a 10.7-year longitudinal cohort study
Authors: Cai Guoqi , Jiang Matthew , Cicuttini Flavia , Jones Graeme
Published: December 2019

Background

To describe the association of age, sex and body mass index with the rate of change of tibial knee cartilage volume over 10.7 years in a community-based sample of older adults.

Methods

Four hundred and eighty-one participants (49% female, mean age 60.8 years [range 51.1–79.7], 49% had knee pain and 58% radiographic osteoarthritis) were included. Tibial cartilage volume of the right knee was assessed on T1-weighted fat-suppressed 1.5 T MRI at baseline and 10.7 years. Data analyses were performed using linear regression models.

Results

The average rate of loss of cartilage volume was 1.2%/year (range 0.2–3.9%) with all participants losing cartilage volume over the study period. There was a significant association between age and loss of tibial cartilage volume in the medial (0.023%/year, 95% confidence interval [CI] 0.010 to 0.036%, p < 0.001), lateral (0.013%/year, 95% CI 0.003 to 0.023%, p = 0.012) and total tibia (0.018%/year, 95% CI 0.009 to 0.026%, p < 0.001). Higher body mass index at baseline and increases in body mass index over time were associated with a greater tibial cartilage loss at the medial (body mass index at baseline 0.040%/year, 95% CI 0.022 to 0.058%, p < 0.001; increases in body mass index 0.055%/year, 95% CI 0.018 to 0.093%, p = 0.004) but not lateral compartment. No evidence of non-linear relationships was observed. Compared to males, females lost more lateral tibial cartilage with increasing age (0.023%/year, 95% CI 0.003 to 0.043%, p = 0.024 for interaction).

Conclusions

Tibial cartilage volume declines at a faster rate with increasing age and body mass index in both males and females, particularly in the medial compartment. In contrast to the low rate of change in radiographs, our findings suggest that cartilage loss at the tibia is universal in this age group.
Quantification and Modeling of the Interactions of Gamma Radiation with Concrete from Bulk-Scale Observations
Authors: Reches Yonathan
Published: December 2019

The exposure of concrete to gamma radiation gives rise to a set of physical and chemical processes over multiple length scales, from molecular to bulk. The literature includes a number of bulk-scale studies which report the radiogenic heating of concrete and the loss of water (unbound, physically-bound, and/or chemically-bound) due to irradiation. This paper mechanistically quantifies observations by these studies, and presents a continuum framework to model the effects of gamma photons on concrete. A basis is presented for comparing otherwise disparate results in the literature for radiolysis rates. The Stefan–Boltzmann Law, adapted to include a gamma heat source term, reasonably describes radiogenic heating in concrete specimens. In multiple studies, the primary mechanism for dehydration is the loss of liquid water in the pore network of the cement product, rather than of water which is physically or chemically bound in a solid state.
Performance of proximity loggers under controlled field conditions: an assessment from a wildlife ecological and epidemiological perspective
Authors: Triguero-Ocaña Roxana , Vicente Joaquín , Acevedo Pelayo
Published: December 2019

Background

Ecological sciences have, in recent decades, benefited from the ability of proximity loggers (PLs)—i.e. devices that transmit and receive radio signals (UHF)—to quantify intra- and inter-specific interactions. These are used to estimate the frequency of contacts according to a predefined distance between individuals or between individuals and environmental features. The performance of these devices may, however, be potentially affected by several factors, signifying that they require accurate calibration under field conditions in order to correctly interpret the information obtained. We assessed the effect of four relevant factors in ecological and epidemiological studies over the attenuation of radio waves in terms of the received signal strength indicator (RSSI) and contact success rate at a short (3 m) and medium distance (up to 20 m). The factors considered were: height above the ground (0–1 m), the presence/absence of vegetation, the presence/absence of live body mass around the devices, the distance between devices and the overlaid effects of all of them.

Results

The RSSI was found to be an accurate measure of distance, although its precision decreased over greater distances (up to 100 m), with the loss being sharper with vegetation, with body mass and when the devices were located on the ground. The success rate at up to 20 m decreased with distance and was also affected by body mass and vegetation. A probability of contact success of 81% was obtained in the best conditions (without vegetation and body mass) at a distance of 3 m, whereas it was of 56% in the worst conditions.

Conclusions

Our study shows the potential synergistic effects of external factors on the performance of PLs, even when they are used to infer near-contacts. We, therefore, highlight the importance of assessing, for each particular study, the combined effect of non-controllable external factors on the performance of PLs in order to estimate the minimum (best scenario) and maximum (worst scenario) level of underestimation in the field data. The sampling design described here is a cost-effective protocol suitable for this purpose.