bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a clinical diagnostic tool to differentiate multiple myeloma from bone metastasis in patients with destructive bone lesions (MM-BM DDx)
Authors: Phinyo Phichayut , Maihom Titinat , Phanphaisarn Areerak , Kerdsinchai Pakorn , Rattarittamrong Ekarat , Patumanond Jayanton , Pruksakorn Dumnoensun
Published: October 2020

Background

Most patients with destructive bone lesions undergo a comprehensive diagnostic procedure to ensure that proper treatment decisions are pursued. For patients with multiple myeloma, this can lead to delays in diagnosis and treatment initiation. This study was conducted to develop a diagnostic rule that could serve as a tool for early identification of multiple myeloma and promote timely referral of patients to haematologists.

Methods

The clinical prediction rule was developed using a retrospective case-series of patients with multiple myeloma (MM) and those with bone metastasis (BM) at Chiang Mai University Hospital from 2012 to 2015. Multivariable fractional polynomial logistic regression was used to derive a diagnostic model to differentiate between MM and BM patients (MM-BM DDx).

Results

A total of 586 patients (136 MM patients and 450 BM patients) were included. Serum creatinine, serum globulin, and serum alkaline phosphatase were identified as significant indicators for the differentiation of MM and BM patients. The MM-BM DDx model showed excellent discriminative ability [AuROC of 0.90 (95%CI 0.86 to 0.93)] and good calibration.

Conclusions

This MM-BM DDx model could potentially allow for early myeloma diagnosis and improvement of overall prognosis. A prospective validation study is needed to confirm the accuracy of the MM-BM DDx model prior to its application in clinical practice.
The role of circulating microRNAs for the diagnosis of hepatitis B virus-associated hepatocellular carcinoma with low alpha-fetoprotein level: a systematic review and meta-analysis
Authors: Peng Cheng , Li Zhuonan , Xie Zishan , Wang Zhanpeng , Ye Yanshuo , Li Bo , Li Wei
Published: October 2020

Background

Alpha-fetoprotein (AFP) has been widely used for many years as a serum marker for hepatocellular carcinoma (HCC). However, AFP has been recognized as having poor sensitivity. More and more studies have concluded that circulating microRNAs (miRNAs) might be a promising biomarker that could complement AFP. However, the diagnostic ability of circulating miRNAs has varied among the studies. Therefore, we performed the present meta-analysis to appraise the diagnostic performance of circulating miRNAs as a biomarker for hepatitis B virus-associated HCC (HBV-HCC) patients with low AFP levels.

Methods

We performed a systematic review and meta-analysis of the published literature to assess the diagnostic accuracy of circulating miRNAs in differentiating HBV-HCC patients with low AFP levels from non-HCC controls.

Results

Circulating miRNAs showed promising potential in the diagnosis of HBV-HCC patients with low AFP levels. In the low-AFP HBV-HCC patients, the area under the curve (AUC) was 0.88 (95% confidence interval [CI]: 0.84–0.90). The pooled sensitivity and specificity were 0.84 (95% CI: 0.78–0.88) and 0.76 (95% CI: 0.69–0.83), respectively.

Conclusions

The detection of circulating miRNAs provides a valuable method for the diagnosis of HBV-HCC in patients with low AFP levels.
Distinct clinicopathological differences between early gastric cardiac and non-cardiac carcinomas: a single-center retrospective study of 329 radical resection cases
Authors: Wang Yaohui , Li Xiuqing , Gao Lili , Wang Chenxi , Zhang Yifen , Huang Qin
Published: October 2020

Background

Early gastric carcinoma is heterogeneous and can be divided into early gastric cardiac carcinoma (EGCC) and early gastric non-cardiac carcinoma (EGNCC) groups. At present, differences in clinicopathology remains obscure between EGCC and EGNCC fundus–corpus and antrum–angularis–pylorus subgroups, especially between EGCC with and without oesophageal invasion.

Methods

In this study, we studied 329 consecutive early gastric carcinoma radical gastrectomies with 70 EGCCs and 259 EGNCCs.

Results

Compared to the EGNCC antrum–angularis–pylorus (n = 181), but not fundus–corpus (n = 78), sub-group, EGCC showed significantly older age, lower prevalence of the grossly depressed pattern, better tumor differentiation, higher percentage of tubular/papillary adenocarcinoma, but lower frequency of mixed poorly cohesive carcinoma with tubular/papillary adenocarcinoma, and absence of lymph node metastasis (LNM) in tumors with invasion up to superficial submucosa (SM1). In contrast, pure poorly cohesive carcinoma was less frequently seen in EGCCs than in EGNCCs, but mixed poorly cohesive carcinoma with tubular/papillary adenocarcinomas was significantly more common in the EGNCC antrum–angularis–pylorus sub-group than in any other group. No significant differences were found between EGCC and EGNCC sub-groups in gender, tumor size, H. pylori infection rate, and lymphovascular/perineural invasion. EGCC with oesophageal invasion (n = 22), compared to EGCC without (n = 48), showed no significant differences in the H. pylori infection rate and oesophageal columnar, intestinal, or pancreatic metaplasia, except for a higher percentage of the former in size > 2 cm and tubular differentiation.

Conclusions

There exist distinct clinicopathologic differences between EGCC and EGNCC sub-groups; EGCC was indeed of gastric origin. Further investigations with larger samples are needed to validate these findings.
Health care costs of injury in the older population: a prospective multicentre cohort study in the Netherlands
Authors: van der Vlegel Marjolein , Haagsma Juanita A. , Geraerds A. J. L. M. , de Munter Leonie , de Jongh Mariska A. C. , Polinder Suzanne
Published: October 2020

Background

With the ageing population, the number of older trauma patients has increased. The aim of this study was to assess non-surgical health care costs of older trauma patients and to identify which characteristics of older trauma patients were associated with high health care costs.

Methods

Trauma patients aged ≥65 years who were admitted to a hospital in Noord-Brabant, the Netherlands, were included in the Brabant Injury Outcome Surveillance (BIOS) study. Non-surgical in-hospital and up to 24- months post-hospital health care use were obtained from hospital registration data and collected with the iMTA Medical Consumption Questionnaire which patients completed 1 week and 1, 3, 6, 12 and 24 months after injury. Log-linked gamma generalized linear models were used to identify cost-driving factors.

Results

A total of 1910 patients were included in the study. Mean total health care costs per patient were €12,190 ranging from €8390 for 65–69 year-olds to €15,550 for those older than 90 years. Main cost drivers were the post-hospital costs due to home care and stay at an institution. Falls (72%) and traffic injury (15%) contributed most to the total health care costs, although costs of cause of trauma varied with age and sex. In-hospital costs were especially high in patients with high injury severity, frailty and comorbidities. Age, female sex, injury severity, frailty, having comorbidities and having a hip fracture were independently associated with higher post-hospital health care costs.

Conclusions

In-hospital health care costs were chiefly associated with high injury severity. Several patient and injury characteristics including age, high injury severity, frailty and comorbidity were associated with post-hospital health care costs. Both fall-related injuries and traffic-related injuries are important areas for prevention of injury in the older population.
The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial
Authors: Gharebaghi Naser , Nejadrahim Rahim , Mousavi Seyed Jalil , Sadat-Ebrahimi Seyyed-Reza , Hajizadeh Reza
Published: October 2020

Background

Coronavirus disease 2019 (COVID-19) has infected people in many countries worldwide. Discovering an effective treatment for this disease, particularly in severe cases, has become the subject of intense scientific investigation. Therefore, the objective of this study was to evaluate the efficacy of intravenous immunoglobulin (IVIg) in patients with severe COVID-19 infection.

Methods

This study was conducted as a randomized placebo-controlled double-blind clinical trial. Fifty-nine patients with severe COVID-19 infection who did not respond to initial treatments were randomly assigned into two groups. One group received IVIg (human)—four vials daily for 3 days (in addition to initial treatment), while the other group received a placebo. Patients’ demographic, clinical, and select laboratory test results, as well as the occurrence of in-hospital mortality, were recorded.

Results

Among total study subjects, 30 patients received IVIg and 29 patients received a placebo. Demographics, clinical characteristics, and laboratory tests were not statistically different (P > 0.05) between the two groups. The in-hospital mortality rate was significantly lower in the IVIg group compared to the control group (6 [20.0%] vs. 14 [48.3%], respectively;P = 0.025). Multivariate regression analysis demonstrated that administration of IVIg did indeed have a significant impact on mortality rate (aOR = 0.003 [95% CI: 0.001–0.815];P = 0.042).

Conclusions

Our study demonstrated that the administration of IVIg in patients with severe COVID-19 infection who did not respond to initial treatment could improve their clinical outcome and significantly reduce mortality rate. Further multicenter studies with larger sample sizes are nonetheless required to confirm the appropriateness of this medication as a standard treatment.

Trial registration

A study protocol was registered at the Iranian Registry of Clinical Trials (www.IRCT.ir), numberIRCT20200501047259N1. It was registered retrospectively on May 17th, 2020.
Influence of family resources on secondhand smoking in pregnant women: a cross-sectional study in the border and minority urban areas of Northwest China
Authors: Chen Jiangyun , Li Xinhui , Fang Pengqian
Published: October 2020

Background

Pregnant women’s exposure to secondhand smoke is a very serious health issue in China. The purpose of our research is to identify factors that predict the probability of exposure to secondhand smoke among pregnant women from the perspective of a family-based open system.

Methods

From September 2014 to August 2015, Urumqi City, Shihezi City, and Shawan County-level City were sampled according to population characteristics. A revised structured questionnaire based on family resources was adapted for use in this study. Questionnaires were collected via convenience sampling at the hospitals with the largest number of local antenatal clients. A total of 1249 pregnant women of age 18–51 years were investigated. Descriptive statistics were calculated to characterize the participants and study variables. Binary logistic regression was performed to assess the impact of family resources corresponding variables on the likelihood that participants would be exposed to SHS. Both unadjusted and adjusted odds ratios (OR/AOR) [with 95% confidence intervals (CI)] were reported.

Results

The secondhand smoke exposure rate found in this study was 54.6%. Having good knowledge of the dangers of secondhand smoke had no effect on reducing the prevalence of exposure (P > 0.05). Even pregnant women whose husbands who did not use tobacco or never smoked nearby had a risk of exposure to secondhand smoke [adjusted odds ratio (AOR) 1.568, 95% CI 1.205–2.041] when the data were adjusted for age, gravidity, gestational weeks, knowledge of the dangers of secondhand smoke, location, and work status. Home smoking bans were confirmed to be an important protective factor (AOR 1.710, 95% CI 1.549–1.918); however, only one-third (33.5%) of participants reported having a smoking ban at home. Religion (mainly Islam), as a special external family resource, was a protective factor that reduced secondhand smoke exposure in pregnant women (AOR 0.399, 95% CI 0.312–0.510).

Conclusions

The effect of family resources on tobacco control should be considered in the development of effective and enduring strategies for indoor smoking bans and smoking cessation.
microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis
Authors: Liu Beibei , Sun Wei , Gao Wuyue , Li Liqiang , Cao Zhenxue , Yang Xiaohuai , Liu Jianmin , Guo Yuanyuan
Published: October 2020

Background

The downregulation of microRNA (miR)-451a has been reported in bladder cancer (BCa) tissues. Herein, we elucidated the role of miR-451a in BCa with the involvement of DNA methyltransferase 3B (DNMT3B).

Methods

We first screened the differentially expressed miRNAs from the serum of 12 BCa patients and 10 healthy controls in the BCa database GSE113486. Subsequently, we detected miR-451a expression and CpG island methylation of the promoter in BCa cells T24 and 5637 with DNMT3B knockdown. The downstream mRNAs of miR-451a were predicted by bioinformatics and KEGG enrichment analysis. Afterwards, the expression patterns of DNMT3B, miR-451a and erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EPHA2) were altered in BCa cells to test the ability of cell proliferation, apoptosis, migration as well as invasion. Finally, the effect of miR-451a and DNMT3B was evaluated in vivo.

Results

miR-451a was significantly reduced in serum of BCa patients and cell lines. Moreover, the expression of DNMT3B in BCa cells was significantly increased, thus promoting methylation of the miR-451a promoter, resulting in miR-451a inhibition. Additionally, we found that miR-451a targeted and negatively regulated EPHA2, while EPHA2 could activate the PI3K/AKT signaling, driving BCa cell growth and metastasis.

Conclusions

Our study proposed and demonstrated that miR-451a downregulation mediated by DNMT3B is critical for proliferation, migration, and invasion of BCa, which may be beneficial for developing more effective therapies against BCa.
A modified Delphi to define drug dosing errors in pediatric critical care
Authors: Roumeliotis Nadia , Pullenayegum Eleanor , Rochon Paula , Taddio Anna , Parshuram Chris
Published: October 2020

Background

There is no globally accepted definition for dosing error in adult or pediatric practice. The definition of pediatric dosing error varies greatly in the literature. The objective of this study was to develop a framework, informed by a set of principles, for a clinician-based definition of drug dosing errors in critically ill children, and to identify the range that practitioners agree is a dosing error for different drug classes and clinical scenarios.

Methods

We conducted a nationwide three staged modified Delphi from May to December 2019. Expert clinicians included Canadian pediatric intensive care unit (PICU) physicians, pharmacists and nurses, with a least 5 years’ experience. Outcomes were underlying principles of drug dosing, and error thresholds, as defined by proportion above and below reference range, for common PICU medications and clinical scenarios.

Results

Forty-four participants met eligibility, and response rates were 95, 86 and 84% for all three rounds respectively. Consensus was achieved for 13 of 15 principles, and 23 of 30 error thresholds. An over-dosed drug that is intercepted, an under-dose of a possibly life-saving medication, dosing 50% above or below target range and not adjusting for a drug interaction were agreed principles of dosing error. Altough there remained much uncertainty in defining dosing error, expert clinicians agreed that, for most medication categories and clinical scenarios, dosing over or below 10% of reference range was considered an error threshold.

Conclusion

Dosing principles and threshold are complex in pediatric critical care, and expert clinicians were uncertain about whether many scenarios were considered in error. For most intermittent medications, dosing over 10% below or above reference range was considered a dosing error, although this was largely influenced by clinical context and drug properties. This consensus driven error threshold will help guide routine clinical dosing practice, standardized reporting and drug quality improvement in pediatric critical care.
Trends and sex disparities in school bullying victimization among U.S. youth, 2011–2019
Authors: Li Ruili , Lian Qiguo , Su Qiru , Li Luhai , Xie Meixian , Hu Jun
Published: October 2020

Background

The prevalence of being bullied traditionally among U.S. high school students is expected to reduce to 17.9%, according to Healthy People 2020 Initiatives. We examined trends in traditional victimization and cybervictimization with the latest large-scale time-series data in the United States.

Methods

We analyzed the data from the 2011–2019 national Youth Risk Behavior Survey (YRBS) to access the trends in traditional victimization and cybervictimization among U.S. high school students. We identified the temporal trends using multivariate logistic regression analyses, accounting for survey design features of YRBS. Participants included 72,605 high school students.

Results

The overall prevalence of victimization was 19.74% for traditional bullying and 15.38% for cyberbullying, suggesting that cyberbullying is not a low frequent phenomenon. The prevalence of victimization ranged from 20.19 to 19.04% for traditional victimization and 16.23 to 14.77% for cybervictimization, and the declined trends for the two kinds of bullying victimization were both statistically non-significant. The degree of overlap between the two kinds of bullying victimization was about 60%. Besides, female students reported more traditional victimization and cybervictimization than male peers within each survey cycle.

Conclusions

No declined trends in traditional victimization and cybervictimization were observed during 2011–2019. Female students are more likely to experience school bullying. To achieve the Healthy People 2020 goal on bullying, more work is needed to explore the underlying reasons behind these unchanging trends.
Effects of gender, activity type, class location and class composition on physical activity levels experienced during physical education classes in British secondary schools: a pilot cross-sectional study
Authors: Delextrat Anne , Esser Patrick , Beale Nick , Bozon Floris , Eldridge Emma , Izadi Hooshang , Johansen-Berg Heidi , Wheatley Catherine , Dawes Helen
Published: October 2020

Background

Pupils in secondary schools do not meet the targets for physical activity levels during physical education (PE) sessions, and there is a lack of data on the vigorous physical activity domain (VPA) in PE known to be positively associated with cardio metabolic health While PE session intensity depends on a variety of factors, the large majority of studies investigating these factors have not taken into account the nested structure of this type of data set. Therefore, the aim of this study was to investigate the relationship between various factors (gender, activity type, class location and class composition) and various activity levels during PE classes in secondary schools, using a multi-level statistical approach.

Methods

Year eight (12–13 years old) adolescents (201 boys and 106 girls) from six schools were fitted with accelerometers during one PE session each, to determine the percentage (%) of the PE session time spent in sedentary (SPA), light (LPA), moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) intensity levels. Two- and three-level (pupils, n = 307; classes, n = 13, schools, n = 6) mixed-effect models were used to assess the relationship between accelerometer-measured physical activity levels (% of class time spent in various activity levels) and gender, activity type, class location and composition.

Results

Participants engaged in MVPA and VPA for 30.7 ± 1.2% and 11.5 ± 0.8% of PE classes, respectively. Overall, no significant association between gender or class composition and PA was shown. A significant relationship between activity type and PA was observed, with Artistic classes significantly less active than Fitness classes for VPA (5.4 ± 4.5 vs. 12.5 ± 7.1%, p = 0.043, d:1.19). We also found a significant association between class location and PA, with significantly less time spent in SPA (24.8 ± 4.8% vs. 30.0 ± 3.4%, p = 0.042, d:0.77) and significantly more time spent in VPA (12.4 ± 3.7% vs. 7.6 ± 2.0%, p = 0.022, d:1.93) and MVPA (32.3 ± 6.7% vs.24.8 ± 3.8%, p = 0.024, d:1.33) in outdoors vs. indoors classes.

Conclusions

The results suggest that class location and activity type could be associated with the intensity of PA in PE. It is essential to take into account the clustered nature of this type of data in similar studies if the sample size allows it.
The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial
Authors: Gjefsen Elisabeth , Bråten Lars Christian Haugli , Goll Guro Løvik , Wigemyr Monica , Bolstad Nils , Valberg Morten , Schistad Elina Iordanova , Marchand Gunn Hege , Granviken Fredrik , Selmer Kaja Kristine , Froholdt Anne , Haugen Anne Julsrud , Dagestad Magnhild Hammersland , Vetti Nils , Bakland Gunnstein , Lie Benedicte Alexandra , Haavardsholm Espen A. , Nilsen Aksel Thuv , Holmgard Thor Einar , Kadar Thomas Istvan , Kvien Tore , Skouen Jan Sture , Grøvle Lars , Brox Jens Ivar , Espeland Ansgar , Storheim Kjersti , Zwart John Anker
Published: October 2020

Background

Low back pain is common and a significant number of patients experience chronic low back pain. Current treatment options offer small to moderate effects. Patients with vertebral bone marrow lesions visualized as Modic changes on magnetic resonance imaging may represent a subgroup within the low back pain population. There is evidence for inflammatory mediators being involved in development of Modic changes; hence, suppression of inflammation could be a treatment strategy for these patients. This study examines the effect of anti-inflammatory treatment with the TNF-α inhibitor infliximab in patients with chronic low back pain and Modic changes.

Methods/design

The BackToBasic trial is a multicenter, double blind, randomized controlled trial conducted at six hospitals in Norway, comparing intravenous infusions with infliximab with placebo. One hundred twenty-six patients aged 18–65 with chronic low back pain and type 1 Modic changes will be recruited from secondary care outpatients’ clinics. The primary outcome is back pain-specific disability at day 154 (5 months). The study is designed to detect a difference in change of 10 (SD 18) in the Oswestry Disability Index at day 154/ 5 months. The study also aims to refine MRI-assessment, investigate safety and cost-effectiveness and explore the underlying biological mechanisms of Modic changes.

Discussion

Finding treatments that target underlying mechanisms could pose new treatment options for patients with low back pain. Suppression of inflammation could be a treatment strategy for patients with low back pain and Modic changes. This paper presents the design of the BackToBasic study, where we will assess the effect of an anti-inflammatory treatment versus placebo in patients with chronic low back pain and type 1 Modic changes.

The study is registered at ClinicalTrials.gov under the identifier NCT03704363. The EudraCT Number: 2017–004861-29.
Effect of a telemedicine intervention for diabetes-related foot ulcers on health, well-being and quality of life: secondary outcomes from a cluster randomized controlled trial (DiaFOTo)
Authors: Iversen Marjolein M. , Igland Jannicke , Smith-Strøm Hilde , Østbye Truls , Tell Grethe S. , Skeie Svein , Cooper John G. , Peyrot Mark , Graue Marit
Published: October 2020

Background

Follow-up care provided via telemedicine (TM) is intended to be a more integrated care pathway to manage diabetes-related foot ulcers (DFU) than traditionally-delivered healthcare. However, knowledge of the effect of TM follow-up on PROMs including self-reported health, well-being and QOL in patients with DFUs is lacking and often neglected in RCT reports in general. Therefore, in this study of secondary outcomes from the DiaFOTo trial, the aim was to compare changes in self-reported health, well-being and QOL between patients with DFUs receiving telemedicine follow-up care in primary healthcare in collaboration with specialist healthcare, and patients receiving standard outpatient care.

Methods

The current study reports secondary endpoints from a cluster randomized controlled trial whose primary endpoint was ulcer healing time. The trial included 182 adults with diabetes-related foot ulcers (94/88 in the telemedicine/standard care groups) in 42 municipalities/districts, recruited from three clinical sites in Western Norway. Mean (SD) diabetes duration for the study population was 20.8 (15.0). The intervention group received care in the community in collaboration with specialist healthcare using an asynchronous telemedicine intervention. The intervention included an interactive web-based ulcer record and a mobile phone enabling counseling and communication between the community nurses and specialist healthcare; the control group received standard outpatient care. In total 156 participants (78/78) reported on secondary endpoints: self-reported health, well-being and quality of life evaluated by generic and disease-specific patient-reported outcome measures (e.g. Euro-QOL, the Hospital Anxiety and Depression Scale (HADS), Problem Areas in Diabetes (PAID), Neuropathy and Foot Ulcer–Specific Quality of Life Instrument (NeuroQOL)). Linear mixed-effects regression was used to investigate possible differences in changes in the scores between the intervention and control group at the end of follow-up.

Results

In intention to treat analyses, differences between treatment groups were small and non-significant for the health and well-being scale scores, as well as for diabetes-related distress and foot ulcer-specific quality of life.

Conclusions

There were no significant differences in changes in scores for the patient reported outcomes between the intervention and control group, indicating that the intervention did not affect the participants’ health, well-being and quality of life.

Trial registration

Clinicaltrials.gov, NCT01710774. Registered October 19th, 2012.
Medical status of patients presenting for treatment at an Australian dental institute: a cross-sectional study
Authors: Frydrych Agnieszka M. , Parsons Richard , Kujan Omar
Published: October 2020

Background

Individuals seeking dental treatment often present with medical conditions which may affect dental treatment provision. The purpose of this study was to determine the prevalence of medical conditions and medication use among individuals attending dental clinics at a Western Australian tertiary institution.

Methods

This observational study examined the general demographics, medical and social histories of 873 subjects presenting for a general dental examination at a Western Australian Tertiary Institution between March 2018 and February 2019. Individual recruited were those presenting to the clinics either as new patients to the Centre or returning patients after an extended period of absence.

Results

Presence of a medical condition was reported by 86% of the participants, with males more commonly affected (p = 0.0448). Medication use was noted by 80% of the participants. Cardiovascular disease (37.9%), allergy (32.3%), mental health disorders (29.4%), musculoskeletal (23.0%), endocrine (22.4%) and respiratory disease (17.8%) were the most common conditions identified. Women were significantly more likely to report allergy (p = 0.0002) or a mental health condition (p = 0.0368).

Conclusion

Medical comorbidities are common among individuals presenting for student dental treatment in Western Australia, highlighting the importance of knowledge and teaching of internal medicine and its application to the dental setting.
High-throughput sequencing identification of differentially expressed microRNAs in metastatic ovarian cancer with experimental validations
Authors: Gu Yang , Zhang Shulan
Published: October 2020

Background

Ovarian cancer (OC) is a common gynecological cancer and characterized by high metastatic potential. MicroRNAs (miRNAs, miRs) have the promise to be harnessed as prognostic and therapeutic biomarkers for OC. Herein, we sought to identify differentially expressed miRNAs and mRNAs in metastatic OC, and to validate them with functional experiments.

Methods

Differentially expressed miRNAs and mRNAs were screened from six pairs of primary OC tissues and metastatic tissues using a miRStar™ Human Cancer Focus miRNA and Target mRNA PCR Array. Then, gene expression profiling results were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The binding affinity between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. Expression of miR-7-5p and TGFβ2 was manipulated to assess their roles in malignant phenotypes of highly metastatic HO-8910PM cells.

Results

MiRNA profiling and sequencing identified 12 miRNAs and 10 mRNAs that were differentially expressed in metastatic tissues. Gene ontology and Pathway analyses determined that 3 differentially expressed mRNAs (ITGB3, TGFβ2 and TNC) were related to OC metastasis. The results of RT-qPCR confirmed that the decrease of miR-7-5p was most significant in OC metastasis, while TGFβ2 was up-regulated in OC metastasis. Moreover, miR-7-5p targeted and negatively regulated TGFβ2. MiR-7-5p overexpression accelerated HO-8910PM cell viability and invasion, and TGFβ2 overexpression reversed the results. Meanwhile, simultaneous miR-7-5p and TGFβ2 overexpression rescued the cell activities.

Conclusions

This study characterizes differentially expressed miRNAs and mRNAs in metastatic OC, where miR-7-5p and its downstream target were most closely associated with metastatic OC. Overexpression of miR-7-5p targets and inhibits TGFβ2 expression, thereby inhibiting the growth and metastasis of OC.
A high prevalence of multi-drug resistant Gram-negative bacilli in a Nepali tertiary care hospital and associated widespread distribution of Extended-Spectrum Beta-Lactamase (ESBL) and carbapenemase-encoding genes
Authors: Manandhar Sulochana , Zellweger Raphael M. , Maharjan Nhukesh , Dongol Sabina , Prajapati Krishna G. , Thwaites Guy , Basnyat Buddha , Dixit Sameer Mani , Baker Stephen , Karkey Abhilasha
Published: October 2020

Background

Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Data on circulating antimicrobial resistance (AMR) genes in Gram-negative bacteria and their correlation with MDR and ESBL phenotypes from Nepal is scarce.

Methods

A retrospective study was performed investigating the distribution of ESBL and carbapenemase genes and their potential association with ESBL and MDR phenotypes in E. coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. isolated in a major tertiary hospital in Kathmandu, Nepal, between 2012 and 2018.

Results

During this period, the hospital isolated 719 E. coli, 532 Klebsiella spp., 520 Enterobacter spp. and 382 Acinetobacter spp.; 1955/2153 (90.1%) of isolates were MDR and half (1080/2153) were ESBL producers. Upon PCR amplification, blaTEM (1281/1771; 72%), blaCTXM-1 (930/1771; 53%) and blaCTXM-8 (419/1771; 24%) were the most prevalent ESBL genes in the enteric bacilli. BlaOXA and blaOXA-51 were the most common blaOXA family genes in the enteric bacilli (918/1771; 25%) and Acinetobacter spp. (218/382; 57%) respectively. Sixteen percent (342/2153) of all isolates and 20% (357/1771) of enteric bacilli harboured blaNDM-1 and blaKPC carbapenemase genes respectively. Of enteric bacilli, Enterobacter spp. was the most frequently positive for blaKPC gene (201/337; 60%). The presence of each blaCTX-M and blaOXA were significantly associated with non-susceptibility to third generation cephalosporins (OR 14.7, p < 0.001 and OR 2.3, p < 0.05, respectively).The presence of each blaTEM, blaCTXM and blaOXA family genes were significantly associated with ESBL positivity (OR 2.96, p < 0.001; OR 14.2, p < 0.001 and OR 1.3, p < 0.05 respectively) and being MDR (OR 1.96, p < 0.001; OR 5.9, p < 0.001 and OR 2.3, p < 0.001 respectively).

Conclusions

This study documents an alarming level of AMR with high prevalence of MDR ESBL- and carbapenemase-positive ESKAPE microorganisms in our clinical setting. These data suggest a scenario where the clinical management of infected patients is increasingly difficult and requires the use of last-resort antimicrobials, which in turn is likely to intensify the magnitude of global AMR crisis.
Preparation and of PVA-based compositions with embedded silver, copper and zinc oxide nanoparticles and assessment of their antibacterial properties
Authors: Pulit-Prociak Jolanta , Staroń Anita , Staroń Paweł , Chmielowiec-Korzeniowska Anna , Drabik Agata , Tymczyna Leszek , Banach Marcin
Published: October 2020

A series of poly(vinyl alcohol) (PVA) based liquid compositions with addition of zinc oxide, silver and copper nanoparticles has been prepared. The compositions also contained other consistency-forming organic components. The physico-chemical properties of the products have been determined. Their pH and density have been assessed. Also, the size of nanoparticles has been defined with using a dynamic light scattering technique. The compositions were subjected to XRD, FT-IR and microscopic analysis as well. Thanks to the incorporation of both metal oxide and metallic nanoparticles, it was possible to enrich the products with antibacterial properties. Their inhibiting properties in the growth of microorganisms have been confirmed against both Gram-negative and Gram-positive strains such as E. coli, S. aureus and P. aeruginosa. Thanks to the ability for solidification, the compositions may be applied on a bacterially contaminated surface, and after destroying the microorganisms and its solidification, it may be peeled off along with the dead bacterial film.
Early evidence of efficacy for orally administered SPM-enriched marine lipid fraction on quality of life and pain in a sample of adults with chronic pain
Authors: Callan Nini , Hanes Doug , Bradley Ryan
Published: October 2020

Background

Marine lipids contain omega-3 fatty acids that can be metabolized into anti-inflammatory and pro-resolving mediators—namely 17-HDHA and 18-HEPE—which can serve as modulators of the pain experience. The purpose of this study was to determine the impact of 4 weeks of oral supplementation with a fractionated marine lipid concentration, standardized to 17-HDHA and 18-HEPE, on health-related quality of life and inflammation in adults with chronic pain.

Methods

This study was a prospective, non-randomized, open-label clinical trial. Forty-four adults with ≥ moderate pain intensity for at least 3 months were recruited. The primary outcome was change in health-related quality of life (QOL) using the Patient Reported Outcomes Measurement Information System-43 Profile (PROMIS-43) and the American Chronic Pain Association (ACPA) QOL scale. Exploratory outcomes assessed safety and tolerability, changes in anxiety and depression, levels of pain intensity and interference, patient satisfaction, and impression of change. Changes in blood biomarkers of inflammation (hs-CRP and ESR) were also explored.

Results

Outcome measures were collected at Baseline, Week 2, and Week 4 (primary endpoint). At Week 4, PROMIS-43 QOL subdomains changed with significance from baseline (p < 0.05), with borderline changes in the ACPA Quality of Life scale (p < 0.052). Exploratory analyses revealed significant changes (p < 0.05) in all measures of pain intensity, pain interference, depression, and anxiety. There were no statistically significant changes in either hs-CRP or ESR, which stayed within normal limits.

Conclusion

We conclude that oral supplementation with a fractionated marine lipid concentration standardized to 17-HDHA and 18-HEPE may improve quality of life, reduce pain intensity and interference, and improve mood within 4 weeks in adults with chronic pain. The consistency and magnitude of these results support the need for placebo-controlled clinical trials of marine lipid concentrations standardized to 17-HDHA and 18-HEPE.

Trial registration ClinicalTrials.gov: Influence of an Omega-3 SPM Supplement on Quality of Life, NCT02683850. Registered 17 February 2016—retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02683850.
NFATc2-dependent epigenetic upregulation of CXCL14 is involved in the development of neuropathic pain induced by paclitaxel
Authors: Liu Meng , Zhang Su-Bo , Luo Yu-Xuan , Yang Yan-Ling , Zhang Xiang-Zhong , Li Bo , Meng Yan , Chen Yuan-Jie , Guo Rui-Xian , Xiong Yuan-Chang , Xin Wen-Jun , Li Dai
Published: October 2020

Background

The major dose-limiting toxicity of paclitaxel, one of the most commonly used drugs to treat solid tumor, is painful neuropathy. However, the molecular mechanisms underlying paclitaxel-induced painful neuropathy are largely unclarified.

Methods

Paw withdrawal threshold was measured in the rats following intraperitoneal injection of paclitaxel. The qPCR, western blotting, protein or chromatin immunoprecipitation, ChIP-seq identification of NFATc2 binding sites, and microarray analysis were performed to explore the molecular mechanism.

Results

We found that paclitaxel treatment increased the nuclear expression of NFATc2 in the spinal dorsal horn, and knockdown of NFATc2 with NFATc2 siRNA significantly attenuated the mechanical allodynia induced by paclitaxel. Further binding site analysis utilizing ChIP-seq assay combining with gene expression profile revealed a shift of NFATc2 binding site closer to TTS of target genes in dorsal horn after paclitaxel treatment.

We further found that NFATc2 occupancy may directly upregulate the chemokine CXCL14 expression in dorsal horn, which was mediated by enhanced interaction between NFATc2 and p300 and consequently increased acetylation of histone H4 in CXCL14 promoter region. Also, knockdown of CXCL14 in dorsal horn significantly attenuated mechanical allodynia induced by paclitaxel.

Conclusion

These results suggested that enhanced interaction between p300 and NFATc2 mediated the epigenetic upregulation of CXCL14 in the spinal dorsal horn, which contributed to the chemotherapeutic paclitaxel-induced chronic pain.
Barley yellow dwarf virus-GAV-derived vsiRNAs are involved in the production of wheat leaf yellowing symptoms by targeting chlorophyll synthase
Authors: Shen Chuan , Wei Caiyan , Li Jingyuan , Zhang Xudong , Zhong Qinrong , Li Yue , Bai Bixin , Wu Yunfeng
Published: October 2020

Background

Wheat yellow dwarf virus disease is infected by barley yellow dwarf virus (BYDV), which causes leaf yellowing and dwarfing symptoms in wheat, thereby posing a serious threat to China's food production. The infection of plant viruses can produce large numbers of vsiRNAs, which can target host transcripts and cause symptom development. However, few studies have been conducted to explore the role played by vsiRNAs in the interaction between BYDV-GAV and host wheat plants.

Methods

In this study, small RNA sequencing was conducted to profile vsiRNAs in BYDV-GAV-infected wheat plants. The putative targets of vsiRNAs were predicted by the bioinformatics software psRNATarget. RT-qPCR and VIGS were employed to identify the function of selected target transcripts. To confirm the interaction between vsiRNA and the target, 5′ RACE was performed to analyze the specific cleavage sites.

Results

From the sequencing data, we obtained a total of 11,384 detected vsiRNAs. The length distribution of these vsiRNAs was mostly 21 and 22 nt, and an A/U bias was observed at the 5′ terminus. We also observed that the production region of vsiRNAs had no strand polarity. The vsiRNAs were predicted to target 23,719 wheat transcripts. GO and KEGG enrichment analysis demonstrated that these targets were mostly involved in cell components, catalytic activity and plant-pathogen interactions. The results of RT-qPCR analysis showed that most chloroplast-related genes were downregulated in BYDV-GAV-infected wheat plants. Silencing of a chlorophyll synthase gene caused leaf yellowing that was similar to the symptoms exhibited by BYDV-GAV-inoculated wheat plants. A vsiRNA from an overlapping region of BYDV-GAV MP and CP was observed to target chlorophyll synthase for gene silencing. Next, 5′ RACE validated that vsiRNA8856 could cleave the chlorophyll synthase transcript in a sequence-specific manner.

Conclusions

This report is the first to demonstrate that BYDV-GAV-derived vsiRNAs can target wheat transcripts for symptom development, and the results of this study help to elucidate the molecular mechanisms underlying leaf yellowing after viral infection.
Rapid point-of-care detection of SARS-CoV-2 using reverse transcription loop-mediated isothermal amplification (RT-LAMP)
Authors: Mautner Lena , Baillie Christin-Kirsty , Herold Heike Marie , Volkwein Wolfram , Guertler Patrick , Eberle Ute , Ackermann Nikolaus , Sing Andreas , Pavlovic Melanie , Goerlich Ottmar , Busch Ulrich , Wassill Lars , Huber Ingrid , Baiker Armin
Published: October 2020

Background

Fast, reliable and easy to handle methods are required to facilitate urgently needed point-of-care testing (POCT) in the current coronavirus pandemic. Life-threatening severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world, infecting more than 33,500,000 people and killing over 1 million of them as of October 2020. Infected individuals without any symptoms might still transfer the virus to others underlining the extraordinary transmissibility of this new coronavirus. In order to identify early infections effectively, treat patients on time and control disease spreading, rapid, accurate and onsite testing methods are urgently required.

Results

Here we report the development of a loop-mediated isothermal amplification (LAMP) based method to detect SARS-CoV-2 genes ORF8 and N directly from pharyngeal swab samples. The established reverse transcription LAMP (RT-LAMP) assay detects SARS-CoV-2 directly from pharyngeal swab samples without previous time-consuming and laborious RNA extraction. The assay is sensitive and highly specific for SARS-CoV-2 detection, showing no cross reactivity when tested on 20 other respiratory pathogens. The assay is 12 times faster and 10 times cheaper than routine reverse transcription real-time polymerase chain reaction, depending on the assay used.

Conclusion

The fast and easy to handle RT-LAMP assay amplifying specifically the genomic regions ORF8 and N of SARS-CoV-2 is ideally suited for POCT at e.g. railway stations, airports or hospitals. Given the current pandemic situation, rapid, cost efficient and onsite methods like the here presented RT-LAMP assay are urgently needed to contain the viral spread.
Avoiding unnecessary hospitalisation for patients with chronic conditions: a systematic review of implementation determinants for hospital avoidance programmes
Authors: Sarkies Mitchell , Long Janet C. , Pomare Chiara , Wu Wendy , Clay-Williams Robyn , Nguyen Hoa Mi , Francis-Auton Emilie , Westbrook Johanna , Levesque Jean-Frédéric , Watson Diane E. , Braithwaite Jeffrey
Published: October 2020

Background

Studies of clinical effectiveness have demonstrated the many benefits of programmes that avoid unnecessary hospitalisations. Therefore, it is imperative to examine the factors influencing implementation of these programmes to ensure these benefits are realised across different healthcare contexts and settings. Numerous factors may act as determinants of implementation success or failure (facilitators and barriers), by either obstructing or enabling changes in healthcare delivery. Understanding the relationships between these determinants is needed to design and tailor strategies that integrate effective programmes into routine practice. Our aims were to describe the implementation determinants for hospital avoidance programmes for people with chronic conditions and the relationships between these determinants.

Methods

An electronic search of four databases was conducted from inception to October 2019, supplemented by snowballing for additional articles. Data were extracted using a structured data extraction tool and risk of bias assessed using the Hawker Tool. Thematic synthesis was undertaken to identify determinants of implementation success or failure for hospital avoidance programmes for people with chronic conditions, which were categorised according to the Consolidated Framework for Implementation Research (CFIR). The relationships between these determinants were also mapped.

Results

The initial search returned 3537 articles after duplicates were removed. After title and abstract screening, 123 articles underwent full-text review. Thirteen articles (14 studies) met the inclusion criteria. Thematic synthesis yielded 23 determinants of implementation across the five CFIR domains. ‘Availability of resources’, ‘compatibility and fit’, and ‘engagement of interprofessional team’ emerged as the most prominent determinants across the included studies. The most interconnected implementation determinants were the ‘compatibility and fit’ of interventions and ‘leadership influence’ factors.

Conclusions

Evidence is emerging for how chronic condition hospital avoidance programmes can be successfully implemented and scaled across different settings and contexts. This review provides a summary of key implementation determinants and their relationships. We propose a hypothesised causal loop diagram to represent the relationship between determinants within a complex adaptive system.

Trial registration

PROSPERO 162812
Galuteolin suppresses proliferation and inflammation in TNF-α-induced RA-FLS cells by activating HMOX1 to regulate IKKβ/NF-κB pathway
Authors: Guan Yin , Zhao Xiaoqian , Liu Weiwei , Wang Yue
Published: October 2020

Objective

Galuteolin (Galu) is a substance extracted and purified from honeysuckle. The purpose of this study was to explore the effects of Galu on the TNF-α-induced RA-FLS cells (synoviocytes) and reveal its potential molecular mechanism from the perspectives of anti-apoptosis and anti-inflammation.

Methods

After TNF-α stimulation, cell proliferation of RA-FLS was assessed by CCK-8 assay. TUNEL staining was used to detect the apoptosis. Western blot was used to detect the expressions of Iκκβ, p-p65, p65, p-IκB, IκB, Cleaved-caspase3, Caspase-3, Bcl-2, and Bax. HO-1 were determined by RT-PCR. The contents of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MMP-1 were determined by ELISA.

Results

Galu significantly suppressed cell proliferation in a dose-dependent manner. Additionally, Galu obviously promotes cell apoptosis rate of RA-FLS cells and elevated the expression levels of HO-1, caspase-3, and Bax, while reducing the expression level of Bcl-2. Furthermore, Galu apparently inhibited the levels of Iκκβ, p-p65, and p-IκB. Moreover, Galu also significantly reduced the levels of pro-inflammatory factors IL-1β, IL-6, IL-8, and MMP-1 in RA-FLS cells.

Conclusion

Galuteolin exerts protective effects against TNF-α-induced RA-FLS cells by inhibiting apoptosis and inflammation, which can guide the clinical use of rheumatoid arthritis.