bluuebunny/crossref_metadata_2025 huggingface dataset:
An easy and effective test to evaluate tear film stability as a self diagnosis of dry eye syndrome: Blinking tolerance time (BTT)
Authors: Hwang Hyung Bin , Ku Yong Ho , Kim Eun Chul , Kim Hyun Seung , Kim Man Soo , Hwang Ho Sik
Published: June 2020

Background: To introduce a new diagnostic test, blinking tolerance time (BTT) to evaluate tear film stability. We will compare it with tear break-up time (tBUT) and validate the value of the BTT as a new self-diagnostic tool for assessing tear film instability.Methods: This was a prospective controlled study involving 212 eyes of 106 participants aged 20–79 years. One hundred fourteen eyes of 57 dry eye patients and 98 eyes of 49 healthy subjects were included in the study. All patients and subjects were administered the following diagnostic tests of dry eye disease: Ocular Surface Disease Index, BTT, tBUT, slit lamp examination, corneal stain score, and Schirmer I test (without anesthesia). Patients and subjects were instructed to not to blinking as possible as he or she can after reset blinking. Examiner measure the time interval between reset blinking and next blinking. tBUTou was defined as the mean of the average of three tBUT values in the right and left eyes. Correlations between BTT and tBUTou were also evaluated. To evaluate the diagnostic efficacy of the BTT and tBUT, ROC curves were generated to obtain a cutoff score, and the sensitivities of the tests against the specificity at all possible thresholds were plotted.Results: Spearman’s correlation analysis showed a statistically significant, weakly positive correlation between BTT and tBUTOU (r = 0.447; p=0.000). The intraclass correlation coefficient (ICC) of the tBUT was 0.679 (95% confidence interval [CI]: 0.575–0.765) and the ICC of the BTT was 0.904 (95% CI: 0.867–0.932). The AUC of the tBUTOU was 0.678 and that of the BTT was 0.628. There was no statistically significant difference between these two AUC values (p=0.641). When the cutoff value of BTT was set to 8.1 sec, the sensitivity of the BTT was 63.3% and the specificity was 56.1%.Conclusion: As a simple and new self-diagnostic diagnosis of dry eye, BTT has diagnostic value in clinical practice. The BTT test has a unique advantage in that it can be used for self-diagnostic diagnosis of dry eye. The BTT test can also be widely used in the clinical setting because it is an inexpensive and simple procedure.
Safety and tolerability of oral lisdexamfetamine in adults with methamphetamine dependence: a phase-2 dose-escalation study
Authors: Ezard Nadine , Clifford Brendan , Dunlop Adrian , Bruno Raimondo , Carr Andrew , Liu Zhixin , Siefried Krista , Lintzeris Nicholas
Published: June 2020

Background: Methamphetamine (MA) dependence is a growing global health issue with no effective pharmacotherapy. Lisdexamfetamine (LDX) is approved for use in the treatment of attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder (BED) in doses ranging from 30 to 70mg/day. LDX has a longer duration of action and lower abuse potential than other amphetamines, and presents a promising candidate for agonist-type treatment of MA dependence. People seeking treatment for MA dependence may require doses of LDX higher than used in ADHD and BED. We examined the safety of LDX at 250mg/day among adults with MA dependence, approximately equivalent to previously trialled doses of dexamphetamine. Methods: We conducted a dose-escalating, phase-2, open label, single-group study of oral LDX at two Australian drug treatment services. Eligible participants were MA dependent adults who reported use of MA on at least 14 of the preceding 28 days. Once daily, supervised LDX doses of 100 to 250mg/day were provided as a single-blinded, ascending-descending dose regimen over 8 weeks. The primary outcomes were safety, drug tolerability, and regimen completion at the end of Week 4 (maximum dose). Participants were followed through to Week 12. Secondary outcomes included: change in MA use; craving; withdrawal; severity of dependence; risk behaviour; change in other substance use; medication acceptability; potential for non-prescription use; adherence; and neurocognitive functioning. Results: Fourteen of 16 participants (87.5%) successfully completed the four week escalation regimen to 250mg/day. Two participants withdrew from the trial in the first week. No participant was withdrawn due to adverse events. MA use decreased significantly (p=0.013) from a median of 21 days (IQR: 16-23) to 13 days (IQR: 11-17) over the four week escalation period.Conclusions: LDX at a dose of up to 250 mg/day was safe and well tolerated in this population, with high retention. Larger trials of LDX as a pharmacotherapy for MA dependence are warranted. Trial Registration : Australian and New Zealand Clinical Trials Registry ACTRN12615000391572.
A Novel Method of Constrained Feature Selection by the Measurement of Pairwise Constraints Uncertainty
Authors: Berahmand Kamal , Rostami Mehrdad , Forouzandeh Saman
Published: June 2020

In recent years, with the development of science and technology, there were considerable advances in datasets in various sciences, and many features are also shown for these datasets nowadays. With a high-dimensional dataset, many features are generally redundant and/or irrelevant for a provided learning task, which has adverse effects with regard to computational cost and/or performance. The goal of feature selection over partially labeled data (semi-supervised feature selection) is to choose a subset of available features with the lowest redundancy with each other and the highest relevancy to the target class, which is the same objective as the feature selection over entirely labeled data. By appropriate reduction of the dimensions, in addition to time-cost savings, performance increases as well. In this paper, side information such as pairwise constraint is used to rank and reduce the dimensions. In the proposed method, the authors deal with checking the quality (strength or uncertainty) of the pairwise constraint. Usually, the quality of the pair of constraints on the dimension reduction is not calculated. In the first step, the strength matrix is created through a similarity matrix and uncertainty region. And then, by using the strength and similarity matrices, a new constraint feature selection ranking is proposed. The performance of the presented method was compared to the performance of the state-of-the-art, and well-known semi-supervised feature selection approaches on eight datasets. The findings indicate that the proposed approach improves previous related approaches with respect to the accuracy of constrained clustering. In particular, the numerical results showed that the presented approach improved the classification accuracy by about 3% and reduced the number of selected features by 1%. Consequently, it can be said that the proposed method has reduced the computational complexity of the machine learning algorithm despite increasing the classification accuracy.
Detection of Escherichia albertii in urinary and gastrointestinal infections in Kermanshah, Iran
Authors: Namdari Afshin , Rahimian-zarif Bahareh , Foroughi Azadeh
Published: June 2020

Background

Escherichia albertii (E. albertii) is a Gram-negative and facultative anaerobe bacterium. In recent years, the bacterium has been isolated from the feces of people with gastroenteritis as a pathogen that causes diarrhea. Due to insufficient information on the phenotypic and biochemical characteristics of E. albertii, it is difficult to distinguish it from other species of the Enterobacteriaceae family. This is especially prevalent in the pathotypes of Escherichia coli (E. coli). Moreover, in clinical laboratories, it is mistakenly identified as E. coli or even Hafnia alvei (H. alvei). This study was performed for the first time in Iran to identify E. albertii by PCR method from a sample of urinary and gastrointestinal infections obtained from clinical laboratories in Kermanshah, which were distinguished as E. coli.
Methods

In this study, 60 urinary samples and 40 fecal samples that were identified as E. coli by phenotypic and biochemical methods in clinical laboratories. The samples were re-evaluated in the first step in terms of specific phenotypic and biochemical characteristics of E. coli. Subsequently, DNA was extracted from the isolates by the phenol method. Then, two lysP and mdh genes were detected for E. albertii and the uidA gene for E. coli by PCR using specific primers pairs.
Results

The results obtained from phenotypic and biochemical tests indicated that all samples were consistent with E. coli characteristics. However, findings from PCR showed that out of a total of 100 samples, specific genes of E. coli were identified in 6 samples (6%) and uidA gene in 94 remaining samples (94%). Of these 6 samples, 5 samples were urinary tract infections, and only one was a gastrointestinal infection.
Conclusion

The findings of this study show that E. albertii can be considered as one of the causes of urinary and gastrointestinal infections that are mistakenly identified in clinical laboratories as E. coli.Therefore, the use of molecular methods for accurate and definitive diagnosis of bacteria can be useful.
Long-Term Effectiveness and Safety of Infliximab and Golimumab in Ankylosing Spondylitis Patients from a Canadian Prospective Observational Registry
Authors: Rahman Proton , Starr Michael , Haaland Derek , Bessette Louis , Teo Michelle , Rampakakis Emmanouil , Lehman Allen J , Nantel Francois
Published: June 2020

Background: The objectives of this study were to describe the profile of ankylosing spondylitis (AS) patients treated with either infliximab (IFX) or subcutaneous golimumab (GLM) treatment in Canadian routine care setting along with assessing long-term effectiveness and safety. Methods: AS patients who were eligible for treatment with IFX or subcutaneous GLM as per their respective Canadian product monographs were enrolled into the BioTRAC registry from 2005-2017. The study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in clinical outcomes and acute phase reactants. Safety was evaluated by assessing the incidence of adverse events (AEs) and drug survival rates. Results: A total of 389 IFX- and 421 GLM-treated patients were enrolled. A significant decrease in disease duration at baseline was observed in the IFX cohort, from a median of 8.0 in 2005-2008 to 1.0 years in 2009-2015 (p<0.001). A reduction in baseline BASFI score (p=0.011) and proportion of patients in ASDAS very high disease activity (p=0.004) was also observed over time. Meanwhile, in the GLM cohort, most disease parameters remained similar from 2010-2017.Treatment with both agents significantly improved all disease parameters over time with similar efficacy between the two agents. The incidence of AEs and SAEs were 136 and 131 events/100 PYs and 10.5 and 8.45 events/100 PYs for IFX- and GLM-treated patients, respectively. Conclusion: Both IFX and GLM treatment in AS significantly reduced disease activity in most outcome measures in a similar fashion and were well tolerated in Canadian routine care. Trial Registration: NCT00741793
Barriers and facilitators for transitioning of young people from adolescent clinics to adult ART clinics in Uganda: Unintended consequences of successful adolescent ART clinics
Authors: Mbalinda Scovia Nalugo , Bakeera-Kitaka Sabrina , Amooti Derrick Lusota , Magongo Eleanor Namusoke , Musoke Philippa , Dan Kaye K
Published: June 2020

BackgroundThere is a growing number of adolescents and young adults with HIV who require transfer of care from pediatric/ adolescent clinics to adult ART clinic. Currently, adolescents are largely in the care of pediatricians; but as they grow, they transition to adult HIV clinics. The purpose of this study was to explore the facilitators and barriers of transitioning among adolescents from adolescent clinics to adult ART clinics.MethodAn explorative qualitative approach was utilised for this study. Eighteen focus group discussions were held in nine health facility with (191) adolescents and young people in order to capture their experiences, barriers and facilitators regarding transitioning to adult clinics. The focus group discussions were audio recorded and transcribed. The Silences Framework using thematic approach guided the analysis.Results The key emerging issues were: Care provided in the adolescent clinics, Unfriendly adults, stigma and discrimination, Congestion and long waiting time, health providers in adult clinics were barriers to transitioning. Moving as a cohort, Transition preparation, care in clinics, positive living, support from the guardian and Young adolescent program Support (YAPS) could facilitate readiness and transitioning.ConclusionAdolescents and young people expressed fear to transition to adult clinics mainly because of the perceived better care provided in adolescent clinic, thus constituting a barrier to smooth transition A range of individual, social and health system and services-related factors hindered transitioning. Expectation of transitioning as a group, assurance of similar care as in the adolescent clinic, and guarantees of confidentiality, privacy and autonomy in decision-making for care were perceived as facilitators. There is need to strengthen implementation of age-appropriate care and individualized case management during care transition at all health facilities. Furthermore, the findings suggest the need to create supportive family, peer, and healthcare environments for adolescent transition.
Perceptions of Asha Workers in the Hope Collaborative Care Mental Health Intervention in Rural South India: A Qualitative Analysis
Authors: Bansal Stuti , Sriniva Krishnamachari , Ekstrand Maria L
Published: June 2020

Background:Common mental disorders are responsible for a heavy disease burden in India and are often highly co-morbid with non-communicable diseases like diabetes and cardiovascular disease, which are increasing in prevalence across India as well. There is a severe lack of mental health resources in India, particularly in rural areas. Rural health care is often dependent on ASHA workers (Accredited Social Health Activists), high school-educated village women trained as community health workers. ASHA workers have been effectively involved in a variety of interventions, including a handful targeting mental illness, but perspectives of ASHA workers have been greatly overlooked.Methods:One-on-one qualitative interviews were conducted with 15 ASHA workers, all of whom completed the parent HOPE study, a collaborative-care randomized controlled trial that aims to integrate mental health care into existing primary care systems in rural Karnataka. The 15 ASHA workers in this substudy were asked questions about their role in HOPE, as well as their perspectives on patient health, mental illness, and the HOPE study.Results:ASHA workers mostly had positive interactions with patients, including encouraging them to attend sessions, helping to explain the topics and techniques, and checking in on the patients frequently. Occasionally ASHAs had negative relationships with patients. ASHA workers were able to identify key barriers to treatment and facilitators to treatment. ASHAs claimed that their knowledge about mental illness improved because of the HOPE study, though some gaps remained in their understanding of mental illness etiology and treatment. Overall, ASHA workers viewed the HOPE study as a necessary and effective intervention, and requested that it continue and expand.Conclusions: ASHA workers are important in establishing and maintaining relationships with patients that encourage attendance and participation, and the efforts of ASHAs often help in mitigating common barriers to treatment. Our results show that the beliefs and knowledge of ASHA workers can be changed in regards to mental illness, and ASHAs can become effective advocates for patients. The perspectives of ASHA workers need to be understood in order to understand the complexities of a rural health system that relies on their work, and most effectively help patients.
Influence of maintaining apical patency in post-endodontic pain
Authors: Shubham Snigdha , Nepal Manisha , Mishra Ravish , Dutta Kishor
Published: June 2020

Background
The purpose of this study was to compare postoperative pain between apical patency and non-patency groups and to evaluate the influence of number of visits, vitality of teeth, group of teeth and preoperative pain on post-operative pain.
Methods
One hundred sixty patients were included in the study. Patients were randomly divided into: Group A (n = 80) contained apical patency maintaining group and Group B (n = 80) contained those treated without maintaining apical patency. Each group was subdivided into equal number of patients treated in single visit (n = 40) and multiple visits (n = 40), including vital (n = 20) and non-vital teeth (n = 20) and single- rooted teeth (n = 10) and multiple-rooted teeth (n = 10). Apical patency was maintained with a size 10 K-file during conventional hand filing step-back shaping procedure. Intensity of pain was recorded before treatment and on days 1, 2, and 7 after treatment using a numerical rating scale. Statistical analysis was done using Mann -Whitney U test and Spearman correlation.
Results
There was statistically significant difference (p < 0.05) in postoperative pain scores between the groups on 1st, 2nd and 7th day follow up. Postoperative pain in patency maintaining group was not influenced by number of visit and group of teeth treated. Whereas, vital teeth when patency was maintained in multiple visits root canal treatment post-operative pain was statistically significant (p = 0.02) in day 1 follow up. Pre-operative pain also influenced postoperative pain with statistically significant difference and positive correlation between the groups.
Conclusions
Our study concluded that maintenance of apical patency increased postoperative pain. Post-operative pain was not influenced by number of visits, and group of teeth. However, for patency group, vital tooth treated in multiple visits results in more postoperative in 1st day follow up. In addition, pre-operative pain also has influence on post-operative pain.
Exploring the experiences of stroke patients treated with transcranial magnetic stimulation for upper limb recovery: a qualitative study
Authors: Lieshout Eline van , Jacobs Lilliane , Pelsma Maaike , Dijkhuizen Rick , Visser-Meily Anne
Published: June 2020

Background: Transcranial magnetic stimulation (TMS) treatments have shown promise in improving arm recovery in stroke patients. Currently, little is known about patients’ experiences with TMS treatment, and this lack of knowledge may affect optimal implementation in clinical practice. The aim of this explorative study was to gain insight in the perceived effects and experiences of the design and delivery of a TMS treatment for upper limb recovery from the perspectives of stroke patients. Methods: This qualitative study was conducted as part of a randomized controlled trial (RCT) in a specialized rehabilitation center. Data were collected through face-to-face semi-structured interviews with 13 stroke patients who completed a 10-day TMS intervention for upper limb recovery. The interviews were recorded, transcribed verbatim and analyzed using thematic analysis. Results: The major themes that emerged from the patients’ feedback were the following: physical and psychological experienced effects (receiving something, sense of purpose, and recovery as a motivator), positive experiences (comfort, power of communication and information, interest and curiosity, no burden, no unpleasant aspects), concerns (uncertainty, equipment, logistics), and likeliness to participate in an RCT (personal drive and beliefs, and altruism). Important components related to the positive experience of the design and delivery of the treatment included comfort (i.e. moment of relaxation) and the sensation of a painless treatment without side-effects. Key concerns included uncertainty and anxiety about possible negative consequences and group allocation. Conclusions: This study demonstrates that TMS is well accepted by stroke patients with an upper limb paresis. Besides the expectation of a therapeutic benefit, the patients reported various psychological effects. Positive experiences, such as the provision of a short moment of relaxation each day, could have practical implications for clinical stroke rehabilitation settings aimed at improving patient satisfaction. Explanation about and feedback from routine motor recovery progression monitoring at fixed times post-stroke is also valued by patients. Negative emotions may be limited or avoided by clear, transparent and recurrent information delivery in future trials. Trial registration: NL5952 Registered November 28, 2016.
Impact of investigator initiated trials and industry sponsored trials on medical practice (IMPACT): Rationale and study design
Authors: Nury Edris , Bischoff Karin , Wollmann Katharina , Nitschke Kai , Lohner Szimonetta , Schumacher Martin , Rücker Gerta , Blümle Anette
Published: June 2020

Background
The German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) initiated large research programs to foster high quality clinical research in the academic area. These investigator initiated trials (IITs) cover important areas of medical research and often go beyond the scope of industry sponsored trials (ISTs). The purpose of this project was to understand to what extent results of randomized controlled IITs and ISTs have an impact on medical practice, measured by their availability for decisions in healthcare and their implementation in clinical practice. We aimed to determine study characteristics influencing a trial’s impact such as type of sponsor and place of conduct.
Methods
In a quasi-experimental design, the research impact of the following sub-cohorts was compared: German IITs (funded by DFG and BMBF or by other German non-commercial organizations), international IITs (without German contribution), German ISTs, and international ISTs. Trials included were drawn from the DFG-/BMBF-Websites, the German Clinical Trials Register, and from ClinicalTrials.gov. Research impact was measured as follows: 1) proportion of published trials, 2) time to publication, 3) proportion of publications appropriately indexed in biomedical databases, 4) proportion of openly accessible publications, 5) broadness of publication’s target group, 6) citation by other research articles, especially 7) by systematic reviews or meta-analyses, 8) appearance of publications in clinical practice guidelines, and 9) identifying study characteristics influencing the impact of trials.
Results
We included 691 trials: 120 German IITs, 200 International IITs, 171 German ISTs and 200 International ISTs. The median number of participants was 150, 30% were international trials and 70% national trials, 48% drug-trials and 52% non-drug trials. Overall, 72% of the trials had one pre-defined primary endpoint, 28% two or more (max. 36).
Conclusions
The results of this project deepen our understanding of the impact of biomedical research on clinical practice and healthcare policy, add important insights for the efficient allocation of scarce research resources and may facilitate providing accountability to the different stakeholders involved.
The misalignment of Tunisia's real effective exchange rate via the BEER approach
Authors: Sassi-Tmar Amel
Published: June 2020

This paper adopts the methodology of error correction models on the BEER (Behavioral Equilibrium Exchange Rate) approach to express the Tunisian real effective exchange rate based on-trade openness, the money supply in terms of GDP, and GDP per capita on the period (1975–2017). Indeed, the error correction mechanism confirms one of the convergences of the REER series of its trajectory to its long-term target value and on the other hand, it reflects the success of the monetary and commercial policies exploited to absorb all unpredictable shocks capable of preventing the stability of ERER from its equilibrium value. The empirical results also show the low sensitivity of the REER to monetary and trade shocks.
Microbial adaptation in vertical soil profiles contaminated by antimony smelting plant
Authors: Xu Rui , Sun Xiaoxu , Han Feng , Xiao Enzong , Li Baoqin , Qiu Lang , Song Benru , Yang Zhaohui , Sun Weimin
Published: June 2020

BackgroundSoil microbes play critical roles in the biogeochemical cycling of antimony (Sb) and arsenic (As), and the effects of Sb and As contamination on soil microbiota have been well documented in surface soils (< 0.2 m). However, their effects in deep soils remain poorly understood. This study determined the depth-resolved effects of Sb and As contamination on the microbial adaptation throughout soil profiles (0–2 m) and compared contaminated soil samples to uncontaminated samples.Methods16S rRNA amplicon sequencing and shotgun metagenomic sequencing were employed to investigate the microbial community and their metabolism traits in soil profiles. Co-occurrence network analysis was used to present the pairwise interactions of microbes.ResultsAs soil depth increased, Acidobacteria (18.8%–44.7% from top to bottom, hereafter), Chloroflexi (8.7%–42.4%), Proteobacteria (11.4%–27.1%), and Thaumarchaeota (0.49%–20.17%) were the most variable phyla from surface to deep soil. A set of co-occurrence networks revealed an obvious changing pattern of microbial interactions as soil depth increased. The networks were loosely connected in the heavily contaminated surface soil but gradually recovered and were well connected in the less contaminated deep soil. Results suggested that individual species became more connected with other patterns to perform syntrophic functions in the less contaminated soil depth. Shotgun metagenomic sequencing results indicated that microbial metabolic potential also changed with soil depth. Genes encoding C metabolism pathways were negatively correlated with Sb and As concentrations. A set of arsenic-related genes was enriched by the high Sb and As contamination but reduced with soil depth. ConclusionsSoil depth-resolved characteristics are often many meters deep and their microbial diversity and community structures obviously change along their vertical soil profiles due to different nutrient contents and biomasses. The significance of this study is that it further reveals how the microbial communities and microbial physiological traits respond to different soil profiles contaminated by high concentrations of Sb and As.
A Single-Centre Retrospective Study of Systemic Reactions to Subcutaneous Immunotherapy
Authors: Robertson Kara , Montazeri Nazanin , Shelke Urvashi , Jeimy Samira , Kim Harold
Published: June 2020

Background: Subcutaneous immunotherapy (SCIT) is the standard approach for treating patients with sensitizations to aeroallergens. However, immunotherapy can trigger severe systemic reactions if delivered inappropriately or to high risk patients. We sought to characterize and quantify SCIT systemic reactions requiring epinephrine administration during a 6-year period in a Canadian setting following the recommendations for components and dosages published in the 2010 Canadian Society of Allergy and Clinical Immunology (CSACI) Immunotherapy Manual.Methods: A single centre retrospective chart review was performed for all patients with systemic reactions to subcutaneous immunotherapy requiring intramuscular epinephrine injection between January 2011 and October 2017. Each systemic reaction requiring epinephrine was reviewed for baseline patient characteristics, details of the reaction, and reaction severity. Research ethics approval was obtained through McMaster University.Results: 28 of 380 patients experienced a systemic reaction requiring epinephrine administration, with an incidence rate of 1 per 1,047 injection visits (0.095%). 26 of the 28 reactions occurred within the mandatory 30-minute observation period post allergen immunotherapy. Of the 28 patients that experienced a systemic reaction to SCIT, 11 patients had asthma and 5 patients had a history of possible food allergy. All of the systemic reactions occurred during injections from vial number 4, and five patients reacted to their first shot of a re-ordered serum. 10 of the 28 patients required more than one intramuscular injection of epinephrine, and 20 of 28 patients were transferred to the hospital by ambulance.Conclusions: This is the first Canadian study to review patients with systemic reactions to subcutaneous immunotherapy. Several best practice methods were employed throughout the study to optimize subcutaneous delivery of immunotherapy serum, and our recorded per injection incidence rate for systemic reactions was comparable or below the rate published in similar studies. The recommendations in the CSACI Immunotherapy Manual provide an approach to standardizing prescriptions for SCIT to maximize immunotherapy efficacy and reduce the risk of systemic reactions, though similar studies in larger multicenter settings are needed to confirm these observations. These observations provide important objective information to clinicians about the potential risks for systemic reactions in patients considering SCIT.
Differential Expression Profiles of Long Noncoding RNA and mRNA in Dexamethasone-Induced Apoptosis of Human Bone Marrow Mesenchymal Stem Cells
Authors: Li Tao , Xu Yingxing , Wang Yingzhen , Jiang Yaping
Published: June 2020

Background
Abnormalities in apoptosis, cell cycle, and proliferation of human bone marrow mesenchymal stem cells (hBMSCs) significantly impact bone metabolism and remodeling, and thereby cause various skeletal disorders. Long-term exposure to a high dosage of dexamethasone (Dex) induces apoptosis and inhibits proliferation of mesenchymal stromal cells (MSCs), which are probably the primary causes of osteoporosis (OP) and steroid-induced osteonecrosis of the femoral head (SONFH). However, to date, the exact mechanisms of Dex-induced apoptosis of BMSCs are still poorly defined.
Methods
A microarray was used to identify differentially expressed lncRNA and mRNA in Dex-induced apoptosis of hBMSCs, and bioinformatics was used to further explore the role of these differentially expressed lncRNAs and mRNAs by the coding and noncoding (CNC) network. Furthermore, validation of the microarray results was performed by quantitative real-time PCR (qRT-PCR) analysis.
Results
The microarray analysis identified a total of 137 differentially expressed mRNA (90 up-regulated and 47 down-regulated) and 90 differentially expressed lncRNA (61 up-regulated and 29 down-regulated) in Dex-induced apoptosis of hBMSCs. The differentially expressed mRNA and lncRNA were associated with the regulation of cell apoptosis. Meanwhile, several signaling pathways involved in the regulation of cell apoptosis, including mTOR signaling pathway, Ras signaling pathway, HIF-1 signaling pathway, NF-kappa B signaling pathway, and TGF-beta signaling pathway, also were identified in interaction net of the significant pathways (Path-Net) analysis. Furthermore, the CNC network further identified 78 core regulatory genes involved in the regulation of apoptosis. Besides, validation by qRT-PCR of the key differentially expressed mRNA and lncRNA, reported to be closely related to cell apoptosis, confirmed the reliability of the microarray dataset.
Conclusions
Collectively, we utilized microarray to identify differentially expressed lncRNA and mRNA in Dex-induced apoptotic hBMSCs, and bioinformatics to explore the interaction between the differentially expressed genes. This study demonstrates the molecular mechanisms of Dex-induced apoptosis of hBMSCs and provides a new research direction for the study of the pathogenesis of steroid-induced osteonecrosis of femoral head.
Generalised Cost-Effectiveness Analysis of 159 Health Interventions For The Ethiopian Essential Health Service Package
Authors: Teshome Getachew , Hailu Alemayehu , Stenberg Karin , Johansson Kjell Arne , Norheim Ole Frithjof , Bertram Melanie Y
Published: June 2020

Background: Cost effectiveness was a criterion used to revise Ethiopia’s essential health service package (EHSP) in 2019. However, there are few cost-effectiveness studies from Ethiopia or directly transferable evidence from other low-income countries to inform a comprehensive revision of the Ethiopian EHSP. Therefore, this paper reports average cost-effectiveness ratios (ACERs) of 159 health interventions used in the revision of Ethiopia’s EHSP. Methods: In this study, we estimate ACERs for 77 interventions on reproductive maternal neonatal and child health (RMNCH), infectious diseases and water sanitation and hygiene as well as for 82 interventions on non-communicable diseases. We used the standardised World Health Organization CHOosing Interventions that are Cost Effective methodology for generalised cost-effectiveness analysis. The health benefits of interventions were determined using a population state-transition model, which simulates the Ethiopian population, accounting for births, deaths and disease epidemiology. Healthy life years (HLYs) gained was employed as a measure of health benefits, and we estimated the economic costs of interventions from the health system perspective, including programme overhead and training costs. We used the Spectrum generalised cost-effectiveness analysis tool for data analysis. We did not explicitly apply cost-effectiveness thresholds, but we used US$100 and $1,000 as references to summarise and present the ACER results. Results: We found ACERs ranging from less than US$1 per HLY gained (for family planning) to about US$48,000 per HLY gained (for treatment of stage 4 colorectal cancer). In general, 75% of the interventions evaluated had ACERs of less than US$1,000 per HLY gained. The vast majority (95%) of RMNCH and infectious disease interventions had an ACER of less than US$1,000 per HLY while almost half (44%) of non-communicable disease interventions had an ACER greater than US$1,000 per HLY. Conclusion: The present study shows that several potential cost-effective interventions are available that could substantially reduce Ethiopia’s disease burden if scaled up. The use of the World Health Organization’s generalised cost-effectiveness analysis tool allowed us to rapidly calculate country-specific cost-effectiveness analysis values for 159 health interventions under consideration for Ethiopia’s EHSP.
Current situation and improvement suggestions of COVID-19 close contacts tracking investigation official letter management
Authors: Li zhiqun , Luo Lei , Jing Qinlong , Xu Jianxiong , Zhou Ziyan , Chen Jian , Huang Rende , Li Jianjie
Published: June 2020

Background: This study analyzes the current status of tracking investigation official letter management for 9036 COVID-19 close contacts in Guangzhou,and explains the necessity of establishing a COVID-19 close contacts tracking investigation sharing system. Method: Based on the information obtained from COVID-19's close contacts' tracking investigation official letters from January 21 to March 31 in Guangzhou, the epidemic situation map and flow chart of receiving and sending official letters were drawn, and the observation rate, sampling rate and Turn positive rate of close contacts were calculated. Results: The tracking investigation official letter involved in 31 provinces (municipalities directly under the central government, autonomous regions) and 172 cities, investigation close contacts with 9036: 309 investigation letters were received from the nonlocal case, investigation close contacts with 2790, involved in 30 provinces and 95 cities, medical observation at a rate of 100%, sampling rate 99.56%, turn positive rate was 3.76%; The city of Guangzhou issued 204 official letters of investigation, with 6,246 close contacts, covering 27 provinces and 114 cities. The medical observation rate was 100%, the sampling rate 99.63%, and turn the positive rate of 2.26%. The reply time of the investigation results is within 1-12 hours, and the other 1-3 days. As of March 31, 440 cases of covid-19 were confirmed in Guangzhou (including 92 imported cases), and the tracking coefficient of close contacts was 14.2 (6246 / 440). Conclusion: Guangzhou close contacts tracking investigation official letter management is tight, the prompt detection of the source of infection to control the epidemic situation is significant. However, due to the multiple sources and complicated process of official letters, it is suggested to establish a COVID-19 close contacts tracking and investigation sharing system.
The Application of 0.75% Metronidazole Gel for the Treatment of Chronic Wounds: Two Case Reports and Literature Review
Authors: Si Ruijuan , Han Jing , Zhang Xue , Ji Fang , Yang Xu , Zhang Ju
Published: June 2020

Objective: To explore the application of metronidazole gel in the healing of chronic foot wounds.Methods: On the basis of reviewing the previous literature, routine debridement care and local application of metronidazole gel were applied to two patients with foot wounds and observations of wound healing were made. The wound of patient A was a deep wound, and the wound of patient B was a diabetic foot ulcer complicated by gangrene.Results: The bleeding and exudate of the patient with a deep wound gradually disappeared, and the wound healed. In the patient with the diabetic foot ulcer, the bleeding and exudate decreased. This was followed by the gradual size reduction of the wound and the formation of a scab over the large wound size.Conclusion: Metronidazole gel was effective in wound resolution of anaerobic bacteria infected wounds. It can serve as a way to relieve patients' pain with a promising therapeutic effect. The effectiveness of metronidazole in the treatment of deep wounds and diabetic foot patients requires further and larger-scale research studies to confirm the findings shown here.
Comparison of Forest Stand Condition Between Thinned and Unthinned Blocks Under Collaborative Forest Management of Western Lowlands of Nepal
Authors: Belbase Kajol , Poudel Arun Sharma , Chhetri Sagar Godar
Published: June 2020

BackgroundAfter a successful implementation of community forestry practices, since 2003 collaborative forest management has been implementing in Nepal. Due to naive approaches of managing forest land in Nepal, the information regarding the forest condition under silviculture practices is very low. The purpose of the study was to understand the regeneration status in the harvested plot and make the comparison of crop stands between the thinned and unthinned plot. MethodHarvested, Thinned, and Unthinned block of Tilaurakot Collaborative Forest was chosen for the study. Eccentric circular plots with radii 11.29m was taken for trees, 5.64m for poles, 2.82m for saplings, and 1.78m for seedling was taken to collect data from each of the selected blocks. Altogether, 71 plots were taken from harvested (11), thinned (30), and unthinned (30) block. Results The result shows seedling and sapling in the harvested block were 14,974 and 3,368 per hectare, respectively. Also, the study identified that the number of seedling and sapling in the thinned block were higher than the unthinned block. However, the growing stock and basal area per hectare in the thinned block were lower than the unthinned block. The number of trees per hectare was lesser in the thinned block (86 per ha) than an unthinned block (140 per ha). Similarly, the number of poles per hectare were lesser in the thinned block (346 per ha) than an unthinned block (370 per ha). Also, the important valve index (IVI) of Sal (Shorea robusta) was found more than other species in harvested, thinned, and unthinned blocks. ConclusionsThe study suggest that the condition of regeneration was better after the opening of the canopy and thinning promotes the growth of trees and undergrowth vegetation. Thus, policy makers should give emphasis on using the silvicultural operations in forest management to maintain the forest health.
Treatment patterns and comorbid burden of patients newly diagnosed with multiple sclerosis in the United States
Authors: Kern David , Cepeda M. Soledad
Published: June 2020

Background: The treatment landscape for multiple sclerosis (MS) is quickly evolving. Understanding real-world treatment patterns of patients is necessary to identifying potential gaps in care.Methods: Patients with incident MS were identified from a large national claims database during 1/1/2014-6/30/2019. Patients had ≥2 diagnoses for MS or an inpatient hospitalization with a primary diagnosis of MS. Patients were required to have enrollment in the database ≥1 year prior to and ≥1 year following their first MS diagnosis. Treatment sequences were captured for all available disease modifying therapies (DMTs) during all available follow-up. Presence of comorbid conditions were captured during the one year prior to and following (and including) the index date; absolute change in prevalence from the pre- to post-index periods was calculated. Results: We identified 5,691 patients with incident MS. Common comorbidities included physical symptoms (e.g., pain, weakness, fatigue), mental health conditions (anxiety, depression), and cardiovascular/metabolic conditions (hypertension, hyperlipidemia, diabetes, obesity). Just 1,994 (35.0%) of patients received a DMT at any time during follow-up. Of those receiving a DMT, 28.2% went on to receive a second line of therapy, 5.8% received a third, and just 0.9% went on to a fourth line. Use of more than one DMT concomitantly occurred in just 1.8% of all treated patients. Glatiramer and dimethyl fumarate were by far the most common first-line treatments received accounting for nearly 62% of patients receiving a DMT. Conclusion: Approximately one-third of patients newly diagnosed with MS received a DMT and the disease is accompanied by a significant comorbid burden.
Risk Factors for Neonatal Bronchopulmonary Dysplasia in Extremely Preterm Premature Rupture of Membranes: A Retrospective Study
Authors: Nakamura Eishin , Matsunaga Shigetaka , Ono Yoshihisa , Takai Yasushi , Seki Hiroyuki
Published: June 2020

Background:Determination of the optimal timing for termination of pregnancy in cases of preterm premature rupture of membranes (pPROM) during the extremely preterm period is still difficult. Bronchopulmonary dysplasia (BPD) is a major disease widely taken into account when determining the prognosis of respiratory disorders in a neonate. Many aspects of this disease remain unclear. With the aim of further improving the prognosis of neonates born to mothers with pPROM, this study examined cases who were diagnosed with pPROM before 28 weeks of gestation. The study analysed risk factors for neonatal BPD and the optimal timing for termination of pregnancy in pPROM cases.Methods:Subjects were 73 cases of single pregnancy who were diagnosed with pPROM during the period from 22 weeks and 0 days to 27 weeks and 6 days of gestation. The following factors were retrospectively examined: the gestational week at which a diagnosis of pPROM was made; the gestational week at which delivery occurred; the period for which the volume of amniotic fluid was maintained; and neonatal BPD as a complication. A receiver operating characteristic (ROC) curve was drawn in order to analyse the relationship between the duration of oligohydramnios and the onset of BPD.ResultsThe mean gestational week at which a diagnosis of amniorrhexis was made was 24.5 ± 1.9 weeks (mean ± SD), and that at which delivery occurred was 27.0 ± 3.0 weeks. Fifty-seven cases (78.1%) were diagnosed with oligohydramnios, the mean duration of which was 17.4 ± 20.5 days. The mean birth weight of neonates was 1000 ± 455 g, of which 49 (67.1%) were diagnosed with BPD following birth. No neonates died in this study. Multivariate analysis of various risk factors for the onset of BPD indicated that oligohydramnios is an independent risk factor for BPD. The ROC curve indicated that the cut-off value was 4 days. In this case, the levels of sensitivity and specificity for predicting the onset of neonatal BPD were 0.941 and 0.917 respectively.ConclusionOur findings suggest that oligohydramnios is an independent risk factor for BPD in cases who are diagnosed with pPROM before 28 weeks of gestation.
Novel immune-related genes in the tumor microenvironment with prognostic value in breast cancer
Authors: Tan Wen , Liu Maomao , Wang Liangshan , Guo Yang , Wei Changsheng , Zhang Shuqi , Luo Chengyu , Liu Nan
Published: June 2020

Background
Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical.
Results
The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas were employed to comprehensively evaluate the TME. Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on Gene Ontology (GO) functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. We further analyzed and screened the overlapping genes of the top 3 GO terms and upregulated differentially expressed genes (DEGs). Overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network analyses revealed that the genes of the top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.
Conclusions
High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.