bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal omentin-1 level, quality of life and marital satisfaction in relation to mode of delivery: a prospective cohort study
Authors: Parvanehvar Simin , Tehranian Najmeh , Kazemnejad Anoshirvan , Mozdarani Hossein
Published: March 2020

Background

The purpose of this study was to evaluate the maternal omentin-1 level, quality of life and marital satisfaction of women with cesarean and vaginal delivery.

Methods

This prospective cohort study was conducted on 45 women with elective cesarean delivery and 45 women with vaginal delivery who referred to a public hospital in Tehran, Iran. Maternal omentin-1 level was measured by ELISA kits within 24 h after delivery. The maternal quality of life and marital satisfaction in the third trimester of pregnancy and at 12 weeks postpartum were measured using WHOQOL-BREF and the Kansas marital satisfaction questionnaires, respectively. For making between-groups and within-groups comparison, independent samples t-test, paired samples t-test and chi-square test were applied accordingly.

Results

The level of maternal omentin-1 was reported to be higher in vaginal delivery group compared to the cesarean group (p = 0.02). No significant difference was found in the quality of life between the two groups in the third trimester of pregnancy and at 12 weeks postpartum period. However, women in both groups had lower scores in physical dimension at 12 weeks postpartum compared to the third trimester of their pregnancy [mean ± SD in vaginal group = 59.28 ± 15.5 vs. 64.44 ± 15.05, p = 0.003 and mean ± SD in cesarean group = 60.07 ± 14.84 vs. 66.50 ± 11.32, p <  0.001]. The results of paired samples t-test indicated that women in NVD group had significantly higher psychological wellbeing at 12 weeks postpartum compared to the third trimester of pregnancy [mean ± SD 68.9 ± 16.82 vs. 65.73 ± 16.87, p = 0.001]. There was no significant difference in marital satisfaction between the two groups at 12 weeks postpartum (P = 0.07). The results of paired samples t-test showed that women in CS group had significantly lower marital satisfaction at 12 weeks postpartum compared to the third trimester of pregnancy [mean SD 18.86 ± 2.04 vs. 19.28 ± 1.79, p = 0.01].

Conclusions

Our findings demonstrated that women with NVD had higher omentin-1 level than women with CS. No significant difference was found in quality of life and marital satisfaction between NVD and CS and omentin-1 level. High level of omentin-1 in NVD may act as a protective factor for mother against metabolic disorders.
Combination versus single-agent as palliative chemotherapy for gastric cancer
Authors: Choi Jin-Hyuk , Choi Yong Won , Kang Seok Yun , Jeong Geum Sook , Lee Hyun Woo , Jeong Seong Hyun , Park Joon Seong , Ahn Mi Sun , Sheen Seung Soo
Published: March 2020

Background

Although combination chemotherapy (CC) is generally recommended in recurrent or primary metastatic gastric cancer (RPMGC), the results of randomized trials are conflicting.

Methods

A retrospective review was conducted on 687 RPMGC patients who received palliative chemotherapy. We compared the overall survival (OS) between CC and single-agent chemotherapy (SC) among these patients, and we analyzed the clinicopathological characteristics affecting outcome including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).

Results

Although 521 patients (75.8%) underwent CC, SC was more frequently performed in elderly patients (57.6%) and ECOG performance status (PS) 2 or 3 (65.8%) patients (p < 0.0001, in each case). The median OS of patients who received CC was significantly longer than that of patients who received SC (11 vs. 8 months, p < 0.0001). No difference in OS between CC and SC was observed in elderly patients (p = 0.583), poor PS (p = 0.810), signet ring cell (p = 0.347), palliative surgical resection (p = 0.307), and high PLR (p = 0.120), with a significant interaction between age and type of regimen (p = 0.012). Moreover, there was no difference in OS between CC and SC after propensity score matching (p = 0.322). Multivariate analysis revealed that palliative resection and ≥ second-line chemotherapy were independently associated with favorable OS (p < 0.0001, in each case), whereas poor PS (p = 0.004), signet ring cell (p < 0.0001), peritoneal metastasis (p = 0.04), high NLR (p = 0.001), and high PLR (p = 0.033) were independent prognostic factors of poor OS.

Conclusions

Although CC is the standard of care in RPMGC, SC can be considered a reasonable option in certain subgroups, such as elderly patients.
A protocol for a multicentre, parallel-group, pragmatic randomised controlled trial to evaluate the NEVERMIND system in preventing and treating depression in patients with severe somatic conditions
Authors: Carli Vladimir , Wasserman Danuta , Hadlaczky Gergö , Petros Nuhamin Gebrewold , Carletto Sara , Citi Luca , Dinis Sergio , Gentili Claudio , Gonzalez-Martinez Sergio , Aldo De Leonibus  , Meyer Björn , Ostacoli Luca , Ottaviano Manuel , Ouakinin Silvia , Paradiso Rita , Poli Riccardo , Rocha Isabel , Settanta Carmen , Waldmeyer Maria Teresa Arredondo , Valenza Gaetano , Scilingo Enzo Pasquale
Published: March 2020

Background

Depressive symptoms are common in individuals suffering from severe somatic conditions. There is a lack of interventions and evidence-based interventions aiming to reduce depressive symptoms in patients with severe somatic conditions. The aim of the NEVERMIND project is to address these issues and provide evidence by testing the NEVERMIND system, designed to reduce and prevent depressive symptoms in comparison to treatment as usual.

Methods

The NEVERMIND study is a parallel-groups, pragmatic randomised controlled trial to assess the effectiveness of the NEVERMIND system in reducing depressive symptoms among individuals with severe somatic conditions. The NEVERMIND system comprises a smart shirt and a user interface, in the form of a mobile application. The system is a real-time decision support system, aiming to predict the severity and onset of depressive symptoms by modelling the well-being condition of patients based on physiological data, body movement, and the recurrence of social interactions. The study includes 330 patients who have a diagnosis of myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants are randomised in blocks of ten to either the NEVERMIND intervention or treatment as usual as the control group. Clinical interviews and structured questionnaires are administered at baseline, at 12 weeks, and 24 weeks to assess whether the NEVERMIND system is superior to treatment as usual. The endpoint of primary interest is Beck Depression Inventory II (BDI-II) at 12 weeks defined as (i) the severity of depressive symptoms as measured by the BDI-II. Secondary outcomes include prevention of the onset of depressive symptoms, changes in quality of life, perceived stigma, and self-efficacy.

Discussion

There is a lack of evidence-based interventions aiming to reduce and prevent depressive symptoms in patients with severe somatic conditions. If the NEVERMIND system is effective, it will provide healthcare systems with a novel and innovative method to attend to depressive symptoms in patients with severe somatic conditions.

Trial registration

DRKS00013391. Registered 23 November 2017.
Views of health care professionals and policy-makers on the use of surveillance data to combat antimicrobial resistance
Authors: Al-Haboubi Mustafa , Trathen Andrew , Black Nick , Eastmure Elizabeth , Mays Nicholas
Published: March 2020

Background

Providing healthcare professionals with health surveillance data aims to support professional and organisational behaviour change. The UK Five Year Antimicrobial Resistance (AMR) Strategy 2013 to 2018 identified better access to and use of surveillance data as a key component. Our aim was to determine the extent to which data on antimicrobial use and resistance met the perceived needs of health care professionals and policy-makers at national, regional and local levels, and how provision could be improved.

Methods

We conducted 41 semi-structured interviews with national policy makers in the four Devolved Administrations and 71 interviews with health care professionals in six locations across the United Kingdom selected to achieve maximum variation in terms of population and health system characteristics. Transcripts were analysed thematically using a mix of a priori reasoning guided by the main topics in the interview guide together with themes emerging inductively from the data. Views were considered at three levels - primary care, secondary care and national - and in terms of availability of data, current uses, benefits, gaps and potential improvements.

Results

Respondents described a range of uses for prescribing and resistance data. The principal gaps identified were prescribing in private practice, internet prescribing and secondary care (where some hospitals did not have electronic prescribing systems). Some respondents under-estimated the range of data available. There was a perception that the responsibility for collecting and analysing data often rests with a few individuals who may lack sufficient time and appropriate skills.

Conclusions

There is a need to raise awareness of data availability and the potential value of these data, and to ensure that data systems are more accessible. Any skills gap at local level in how to process and use data needs to be addressed. This requires an identification of the best methods to improve support and education relating to AMR data systems.
The efficacy of recombinant human soluble thrombomodulin (rhsTM) treatment for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis
Authors: Kamiya Hiroyuki , Panlaqui Ogee Mer
Published: March 2020

Background

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is devastating with no established treatment. This phenomenon involves disordered coagulation and excessive inflammatory reactions. As recombinant human soluble thrombomodulin (rhsTM) possesses anti-coagulative and anti-inflammatory properties, the medicine is expected to improve the prognosis of the disease. The aim of this study was to summarize current evidence regarding benefits and harms of rhsTM treatment for AE of IPF.

Method

Patients with AE of IPF were eligible for the review and all of the other types of interstitial pneumonias were excluded. The effect of rhsTM treatment on the outcomes such as all-cause mortality was estimated in comparison to conventional therapy. Primary studies of any design aside from a case report were reviewed. Electronic databases such as Medline and EMBASE were searched from 2002 through August 14, 2019. Two reviewers independently selected eligible reports and extracted relevant data. A risk of bias of individual studies was assessed similarly. Meta-analysis was conducted for univariate results if at least three studies were available for the same outcome.

Result

Out of a total of 390 records identified, eight studies were first deemed eligible and four of them were finally focused for the review. Only one study was a prospective trial and a historical control was employed in all studies. An overall risk of bias was rated as serious in three out of four studies. A total of 169 subjects were included. Two out of three studies that reported 3-month all-cause mortality by univariate analysis demonstrated beneficial effects of rhsTM treatment and a pooled analysis demonstrated that rhsTM treatment improved 3-month all-cause mortality with a risk ratio of 0.50 (95% confidence interval (CI): 0.35–0.72). All two studies reporting multivariate results demonstrated that rhsTM treatment improved 3-month all-cause mortality with odds ratios of 0.21 (95% CI: 0.05–0.91) and 0.25 (95% CI: 0.09–0.68), respectively. There were no serious adverse events.

Conclusion

The rhsTM treatment was demonstrated to improve 3-month all-cause mortality of AE of IPF with no serious adverse events. However, these findings should be interpreted with caution due to a small number of studies and serious risk of bias.
Total resuscitative endovascular balloon occlusion of the aorta causes inflammatory activation and organ damage within 30 minutes of occlusion in normovolemic pigs
Authors: Sadeghi Mitra , Dogan Emanuel M. , Karlsson Christina , Jansson Kjell , Seilitz Jenny , Skoog Per , Hörer Tal M. , Nilsson Kristofer F.
Published: March 2020

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) causes physiological, metabolic, end-organ and inflammatory changes that need to be addressed for better management of severely injured patients. The aim of this study was to investigate occlusion time-dependent metabolic, end-organ and inflammatory effects of total REBOA in Zone I in a normovolemic animal model.

Methods

Twenty-four pigs (25-35 kg) were randomized to total occlusion REBOA in Zone I for either 15, 30, 60 min (REBOA15, REBOA30, and REBOA60, respectively) or to a control group, followed by 3-h reperfusion. Hemodynamic variables, metabolic and inflammatory response, intraperitoneal and intrahepatic microdialysis, and plasma markers of end-organ injuries were measured during intervention and reperfusion. Intestinal histopathology was performed.

Results

Mean arterial pressure and cardiac output increased significantly in all REBOA groups during occlusion and blood flow in the superior mesenteric artery and urinary production subsided during intervention. Metabolic acidosis with increased intraperitoneal and intrahepatic concentrations of lactate and glycerol was most pronounced in REBOA30 and REBOA60 during reperfusion and did not normalize at the end of reperfusion in REBOA60. Inflammatory response showed a significant and persistent increase of pro- and anti-inflammatory cytokines during reperfusion in REBOA30 and was most pronounced in REBOA60. Plasma concentrations of liver, kidney, pancreatic and skeletal muscle enzymes were significantly increased at the end of reperfusion in REBOA30 and REBOA60. Significant intestinal mucosal damage was present in REBOA30 and REBOA60.

Conclusion

Total REBOA caused severe systemic and intra-abdominal metabolic disturbances, organ damage and inflammatory activation already at 30 min of occlusion.
Coexistence and cooperation in structured habitats
Authors: Geyrhofer Lukas , Brenner Naama
Published: March 2020

Background

Natural habitats are typically structured, imposing constraints on inhabiting populations and their interactions. Which conditions are important for coexistence of diverse communities, and how cooperative interaction stabilizes in such populations, have been important ecological and evolutionary questions.

Results

We investigate a minimal ecological framework of microbial population dynamics that exhibits crucial features to show coexistence: Populations repeatedly undergo cycles of separation into compartmentalized habitats and mixing with new resources. The characteristic time-scale is longer than that typical of individual growth. Using analytic approximations, averaging techniques and phase-plane methods of dynamical systems, we provide a framework for analyzing various types of microbial interactions. Population composition and population size are both dynamic variables of the model; they are found to be decoupled both in terms of time-scale and parameter dependence. We present specific results for two examples of cooperative interaction by public goods: collective antibiotics resistance, and enhanced iron-availability by pyoverdine. We find stable coexistence to be a likely outcome.

Conclusions

The two simple features of a long mixing time-scale and spatial compartmentalization are enough to enable coexisting strains. In particular, costly social traits are often stabilized in such an environment—and thus cooperation established.
Assessing the training needs of medical students in patient information gathering
Authors: Gilligan Conor , Brubacher Sonja P. , Powell Martine B.
Published: March 2020

Background

Effective communication is at the heart of good medical practice but rates of error, patient complaints, and poor clinician job satisfaction are suggestive of room for improvement in this component of medical practice and education.

Methods

We conducted semi-structured interviews with experienced clinicians (n = 19) and medical students (n = 20) to explore their experiences associated with teaching and learning clinical communication skills and identify targets for improvements to addressing these skills in medical curricula.

Results

Interviews were thematically analysed and four key themes emerged; the importance of experience, the value of role-models, the structure of a consultation, and confidence.

Conclusions

The findings reinforce the need for improvement in teaching and learning communication skills in medicine, with particular opportunity to target approaches to teaching foundational skills which can establish a strong grounding before moving into more complex situations, thus preparing students for the flexibility required in medical interviewing. A second area of opportunity and need is in the engagement and training of clinicians as mentors and teachers, with the findings from both groups indicating that preparation for teaching and feedback is lacking. Medical programs can improve their teaching of communication skills and could learn from other fields s to identify applicable innovative approaches.
A new instrument to measure high value, cost-conscious care attitudes among healthcare stakeholders: development of the MHAQ
Authors: Mordang Serge B. R. , Könings Karen D. , Leep Hunderfund Andrea N. , Paulus Aggie T. G. , Smeenk Frank W. J. M. , Stassen Laurents P. S.
Published: March 2020

Background

Residents have to learn to provide high value, cost-conscious care (HVCCC) to counter the trend of excessive healthcare costs. Their learning is impacted by individuals from different stakeholder groups within the workplace environment. These individuals’ attitudes toward HVCCC may influence how and what residents learn. This study was carried out to develop an instrument to reliably measure HVCCC attitudes among residents, staff physicians, administrators, and patients. The instrument can be used to assess the residency-training environment.

Method

The Maastricht HVCCC Attitude Questionnaire (MHAQ) was developed in four phases. First, we conducted exploratory factor analyses using original data from a previously published survey. Next, we added nine items to strengthen subscales and tested the new questionnaire among the four stakeholder groups. We used exploratory factor analysis and Cronbach’s alphas to define subscales, after which the final version of the MHAQ was constructed. Finally, we used generalizability theory to determine the number of respondents (residents or staff physicians) needed to reliably measure a specialty attitude score.

Results

Initial factor analysis identified three subscales. Thereafter, 301 residents, 297 staff physicians, 53 administrators and 792 patients completed the new questionnaire between June 2017 and July 2018. The best fitting subscale composition was a three-factor model. Subscales were defined as high-value care, cost incorporation, and perceived drawbacks. Cronbach’s alphas were between 0.61 and 0.82 for all stakeholders on all subscales. Sufficient reliability for assessing national specialty attitude (G-coefficient > 0.6) could be achieved from 14 respondents.

Conclusions

The MHAQ reliably measures individual attitudes toward HVCCC in different stakeholders in health care contexts. It addresses key dimensions of HVCCC, providing content validity evidence. The MHAQ can be used to identify frontrunners of HVCCC, pinpoint aspects of residency training that need improvement, and benchmark and compare across specialties, hospitals and regions.
Yeast display platform technology to prepare oral vaccine against lethal H7N9 virus challenge in mice
Authors: Lei Han , Xie Bowen , Gao Tong , Cen Qianhong , Ren Yi
Published: March 2020

Background

Existing methods for preparing influenza vaccines pose the greatest challenge against highly pandemic avian influenza H7N9 outbreak in the poultry and humans. Exploring a new strategy for manufacturing and delivering a safe and effective H7N9 vaccine is needed urgently.

Results

An alternative approach is to develop an influenza H7N9 oral vaccine based on yeast display technology in a timely manner. Hemagglutinin (HA) of A/Anhui/1/2013 (AH-H7N9) is used as a model antigen and characterized its expression on the surface of Saccharomyces cerevisiae (S.cerevisiae) EBY 100. Mice administrated orally with S.cerevisiae EBY100/pYD5-HA produced significant titers of IgG antibody as well as significant amounts of cytokines IFN-γ and IL-4. Importantly, S.cerevisiae EBY100/pYD5-HA could provide effective immune protection against homologous A/Anhui/1/2013 (AH-H7N9) virus challenge.

Conclusions

Our findings suggest that platform based on yeast surface technology provides an alternative approach to prepare a promising influenza H7N9 oral vaccine candidate that can significantly shorten the preparedness period and result in effective protection against influenza A pandemic.
First evidence of the deletion in the pfhrp2 and pfhrp3 genes in Plasmodium falciparum from Equatorial Guinea
Authors: Berzosa Pedro , González Vicenta , Taravillo Laura , Mayor Alfredo , Romay-Barja María , García Luz , Ncogo Policarpo , Riloha Matilde , Benito Agustín
Published: March 2020

Background

The World Health Organization (WHO) recommends rapid diagnostic tests (RDTs) as a good alternative malaria-diagnosis method in remote parts of sub-Saharan Africa. The majority of commercial RDTs currently available detect the Plasmodium falciparum protein histidine-rich protein 2 (PfHRP2). There have also been recent reports of pfhrp2 gene deletions being found in parasites collected from several African countries. The WHO has concluded that lacking the pfhrp2 gene must be monitored in Africa. The purpose of the study was to analyse why the samples that were positive by PCR were negative by RDTs and, therefore, to determine whether there have been deletions in the pfhrp2 and/or pfhrp3 genes.

Methods

Malaria NM-PCR was carried out on all the samples collected in the field. A group of 128 samples was positive by PCR but negative by RDT; these samples were classified as RDT false-negatives. PCR was carried out for exon2 of pfhrp2 and pfhrp3 genes to detect the presence or absence of these two genes. Frequencies with 95% confidence intervals (CIs) were used for prevalence estimates. Associations were assessed by the Chi square test or Fisher´s exact test. The level of significance was set at p ≤ 0.05. Statistical analyses were performed using the software package SPSSv.15.0.

Results

After PCR, 81 samples were identified (4.7%, 95% CI 3.8–5.8) which had deletion in both genes, pfhrp2 and pfhrp3. Overall, however, 11 samples (0.6%, 95% CI 0.36–1.14) had deletion only in pfhrp2 but not in pfhrp3, and 15 (0.9%, 95% CI 0.6–1.5) presented with deletion only in pfhrp3 but not in pfhrp2. Considering the pfhrp2 gene separately, within the total of 1724 samples, 92 (5.3%, 95% CI 4.37–6.5) had evidence of deletion.

Conclusion

The present study provides the first evidence of deletion in the pfhrp2 and pfhrp3 genes in P. falciparum isolates from Equatorial Guinea. However, larger studies across different regions within the country and across different seasonal profiles are needed to determine the full extent of pfhrp2 and pfhrp3 deletion. It is strongly recommended to implement an active surveillance programme in order to detect any increases in pfhrp2 and pfhrp3 deletion frequencies.
Local health governance in Tajikistan: accountability and power relations at the district level
Authors: Jacobs Eelco , Baez Camargo Claudia
Published: March 2020

Background

Relationships of power, responsibility and accountability between health systems actors are considered central to health governance. Despite increasing attention to the role of accountability in health governance a gap remains in understanding how local accountability relations function within the health system in Central Asia. This study addresses this gap by exploring local health governance in two districts of Tajikistan using principal-agent theory.

Methods

This comparative case study uses a qualitative research methodology, relying on key informant interviews and focus group discussions with local stakeholders. Data analysis was guided by a framework that conceptualises governance as a series of principal-agent relations between state actors, citizens and health providers. Special attention is paid to voice, answerability and enforceability as crucial components of accountability.

Results

The analysis has provided insight into the challenges to different components making up an effective accountability relationship, such as an unclear mandate, the lack of channels for voice or insufficient resources to carry out a mandate. The findings highlight the weak position of health providers and citizens towards state actors and development agents in the under-resourced health system and authoritarian political context. Contestation over resources among local government actors, and informal tools for answerability and enforceability were found to play an important role in shaping actual accountability relations. These accountability relationships form a complex institutional web in which agents are subject to various accountability demands. Particularly health providers find themselves to be in this role, being held accountable by state actors, citizens and development agencies. The latter were found to have established parallel principal-agent relationships with health providers without much attention to the role of local state actors, or strengthening the short accountability route from citizens to providers.

Conclusion

The study has provided insight into the complexity of local governance relations and constraints to formal accountability processes. This has underlined the importance of informal accountability tools and the political-economic context in shaping principal-agent relations. The study has served to demonstrate the use and limitations of agency theory in health governance analysis, and points to the importance of entrenched positions of power in local health systems.
Noncoding RNAs in cancer immunity: functions, regulatory mechanisms, and clinical application
Authors: Zhang Le , Xu Xiaonan , Su Xiulan
Published: March 2020

It is well acknowledged that immune system is deeply involved in cancer initiation and progression, and can exert both pro-tumorigenic and anti-tumorigenic effects, depending on specific microenvironment. With the better understanding of cancer-associated immune cells, especially T cells, immunotherapy was developed and applied in multiple cancers and exhibits remarkable efficacy. However, currently only a subset of patients have responses to immunotherapy, suggesting that a boarder view of cancer immunity is required. Non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are identified as critical regulators in both cancer cells and immune cells, thus show great potential to serve as new therapeutic targets to improve the response of immunotherapy. In this review, we summarize the functions and regulatory mechanisms of ncRNAs in cancer immunity, and highlight the potential of ncRNAs as novel targets for immunotherapy.
Metabolism of pancreatic cancer: paving the way to better anticancer strategies
Authors: Qin Cheng , Yang Gang , Yang Jinshou , Ren Bo , Wang Huanyu , Chen Guangyu , Zhao Fangyu , You Lei , Wang Weibin , Zhao Yupei
Published: March 2020

Pancreatic cancer is currently one of the most lethal diseases. In recent years, increasing evidence has shown that reprogrammed metabolism may play a critical role in the carcinogenesis, progression, treatment and prognosis of pancreatic cancer. Affected by internal or external factors, pancreatic cancer cells adopt extensively distinct metabolic processes to meet their demand for growth. Rewired glucose, amino acid and lipid metabolism and metabolic crosstalk within the tumor microenvironment contribute to unlimited pancreatic tumor progression. In addition, the metabolic reprogramming involved in pancreatic cancer resistance is also closely related to chemotherapy, radiotherapy and immunotherapy, and results in a poor prognosis. Reflective of the key role of metabolism, the number of preclinical and clinical trials about metabolism-targeted therapies for pancreatic cancer is increasing. The poor prognosis of pancreatic cancer patients might be largely improved after employing therapies that regulate metabolism. Thus, investigations of metabolism not only benefit the understanding of carcinogenesis and cancer progression but also provide new insights for treatments against pancreatic cancer.
Role of non-coding RNAs and RNA modifiers in cancer therapy resistance
Authors: Zhang Xinyi , Xie Kai , Zhou Honghua , Wu Yuwei , Li Chan , Liu Yating , Liu Zhaoya , Xu Qian , Liu Shuang , Xiao Desheng , Tao Yongguang
Published: March 2020

As the standard treatments for cancer, chemotherapy and radiotherapy have been widely applied to clinical practice worldwide. However, the resistance to cancer therapies is a major challenge in clinics and scientific research, resulting in tumor recurrence and metastasis. The mechanisms of therapy resistance are complicated and result from multiple factors. Among them, non-coding RNAs (ncRNAs), along with their modifiers, have been investigated to play key roles in regulating tumor development and mediating therapy resistance within various cancers, such as hepatocellular carcinoma, breast cancer, lung cancer, gastric cancer, etc. In this review, we attempt to elucidate the mechanisms underlying ncRNA/modifier-modulated resistance to chemotherapy and radiotherapy, providing some therapeutic potential points for future cancer treatment.
Potential effects of using non-combustible tobacco and nicotine products during pregnancy: a systematic review
Authors: Glover M. , Phillips Carl V.
Published: March 2020

Background

The range of risk reduced alternatives to smoking tobacco is increasing and so is use among pregnant women. The substantial harms of smoking during pregnancy are well established and there is reason to believe that nicotine alone is somewhat harmful. Differences in the exposure chemistry strongly suggest that the effects of using smoke-free nicotine products (including pharmaceutical nicotine products, smokeless tobacco, and electronic cigarettes containing nicotine) fall somewhere in the range between zero risk to the risk from smoking. How much lower risk these consumption choices are in terms of pregnancy outcomes, however, remains uncertain.

Methods

We reviewed the literature on smoke-free nicotine and tobacco product exposure and birth-outcome endpoints. Studies were included if they compared outcomes to either no nicotine use or smoking. We searched Google Scholar using broad search terms and additional articles were snowballed from citations. We report what could be learned from each study, given its methods.

Results

Of the 21 studies reviewed, 12 reported on the use of nicotine replacement therapies, 7 on Swedish snus, 1 on Alaskan iq’mik, and 1 on e-cigarettes. The range of results tends to support the prediction that smoke-free product use during pregnancy probably increases the risk of some negative birth outcomes, but that any effect is less than that from smoking. However, the limitations of epidemiology are such that no more-precise a conclusion is possible.

Discussion

The available epidemiology does not change our prior beliefs, based on other evidence and knowledge, that the risks from smoke-free nicotine and tobacco are lower than those for smoking, though it suggests they are non-zero. However, it also demonstrates that the epidemiology is unlikely to provide precise quantitative estimates. This is not just a matter of lack of studies; given the inherent limitation of these studies, doubling or tripling the corpus of available studies would add little precision. For the foreseeable future, decisions about using these products will need to be made based on rough estimates, based on a variety of forms of evidence, and qualitative comparisons.
Parkinson’s disease with early motor complications: predicting EQ-5D- 3L utilities from PDQ-39 data in the EARLYSTIM trial
Authors: Zahra Mehdi , Durand-Zaleski Isabelle , Górecki Michal , Walleser Autiero Silke , Barnett Gillian , Schüpbach W. M. Michael
Published: March 2020

Background

A utility value is a health-related quality of life metric (HRQoL) metric used in a cost-effectiveness analysis. While utilities as outcomes in the treatment of advanced Parkinson’s disease (PD) with deep brain stimulation (DBS) are available, they do not currently exist for PD with early motor complications. The objectives of this study were to predict utilities from observed disease-specific HRQoL data using two mapping algorithms, and investigate their performance in terms of longitudinal changes within and between treatment groups, and distribution by PD severity.

Methods

This is a post hoc analysis of data from the EARLYSTIM trial of DBS compared with best medical therapy (BMT) in PD patients with early motor complications We used two published algorithms comprising ordinal and multinomial regression models to map EQ-5D-3L utilities from observed PD-specific 39 item Questionnaire (PDQ-39) scores in EARLYSTIM. Utilities were calculated using the predicted functioning levels of EQ-5D-3L dimensions and the established EQ-5D-3L UK tariffs. Statistical analyses (analysis of variance, two-tailed Student’s t-test) were used to test the change from baseline within groups and difference in change from baseline between groups in utilities. Boxplots were developed to investigate the distribution of predicted utilities by PD severity, measured using the Hoehn and Yahr scale.

Results

The change from baseline in predicted mean utilities was statistically significant at all visits up to 24 months for the DBS group (p < 0.001) with both algorithms, and statistically significant at 12 months only (p = 0.04) for the BMT group with one algorithm. With both algorithms, the between-groups difference in change from baseline in predicted mean utilities favored DBS at all follow-up visits (p < 0.001). Based on the Hoehn and Yahr scale, predicted utilities deteriorated with increasing disease severity.

Conclusions

Among PD patients with early motor complications, utilities predicted by both mapping algorithms using PDQ-39 data demonstrated a statistically and clinically meaningful improvement with DBS compared with BMT. It was not possible to conclude if one algorithm was more responsive than other. In the absence of utilities collected directly from patients, mapping is an acceptable option permitting economic evaluations to be undertaken.
Multiple trauma including pelvic fracture with multiple arterial embolization: an autopsy case report
Authors: Miyake Takahito , Okada Hideshi , Kanda Norihide , Yamaji Fuminori , Okamoto Haruka , Ushikoshi Hiroaki , Noguchi Kei , Tomita Hiroyuki , Yoshida Shozo , Ogura Shinji
Published: March 2020

Background

Pelvic fracture with high energy trauma has a high mortality rate, especially in men. In addition, severe multiple trauma, major hemorrhage, and administration of red blood cells predict mortality in elderly patients with pelvic fracture. We herein report a rare case in which multiple arterial embolization occurred after pelvic fracture.

Case presentation

An 83-year-old male cyclist was transported to our hospital after being struck by a car. On arrival, he was diagnosed with multiple trauma, including rib fractures with hemothorax, lumbar fractures of the transverse process, and injuries in the right acetabulum, left adrenal gland, and liver. He underwent massive transfusion and transcatheter arterial embolization due to extravasation from the right superior gluteal artery and left adrenal gland. On the second day, owing to right lower leg ischemia, serum creatinine kinase and myoglobin levels were markedly elevated from the reference value; hence, a right above-knee amputation was performed 12 h after the accident. However, both protein levels remained high after amputation, resulting in acute renal injury, which was treated via hemodiafiltration on hospital day 3. In addition, sustained low efficiency hemodialysis and plasma exchange were performed on hospital day 4. Despite these treatments, the patient’s hemodynamics did not improve, and he died on hospital day 8. The autopsy revealed necropsy of the iliopsoas muscles and the digestive tract.

Conclusions

The causes of the patient’s death were considered to be persistent rhabdomyolysis and severe hypotension due to iliopsoas necrosis and peritonitis due to digestive tract necrosis. Multiple arterial embolization caused by consumption coagulopathy associated with multiple trauma may account for severe outcomes in this case.
Identification of a robust functional subpathway signature for pancreatic ductal adenocarcinoma by comprehensive and integrated analyses
Authors: Wang Ping , Zhang Chunlong , Li Weidong , Zhai Bo , Jiang Xian , Reddy Shiva , Jiang Hongchi , Sun Xueying
Published: March 2020

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy and its mortality continues to rise globally. Because of its high heterogeneity and complex molecular landscapes, published gene signatures have demonstrated low specificity and robustness. Functional signatures containing a group of genes involved in similar biological functions may display a more robust performance.

Methods

The present study was designed to excavate potential functional signatures for PDAC by analyzing maximal number of datasets extracted from available databases with a recently developed method of FAIME (Functional Analysis of Individual Microarray Expression) in a comprehensive and integrated way.

Results

Eleven PDAC datasets were extracted from GEO, ICGC and TCGA databases. By systemically analyzing these datasets, we identified a robust functional signature of subpathway (path:00982_1), which belongs to the drug metabolism-cytochrome P450 pathway. The signature has displayed a more powerful and robust capacity in predicting prognosis, drug response and chemotherapeutic efficacy for PDAC, particularly for the classical subtype, in comparison with published gene signatures and clinically used TNM staging system. This signature was verified by meta-analyses and validated in available cell line and clinical datasets with chemotherapeutic efficacy.

Conclusion

The present study has identified a novel functional PDAC signature, which has the potential to improve the current systems for predicting the prognosis and monitoring drug response, and to serve a linkage to therapeutic options for combating PDAC. However, the involvement of path:00982_1 subpathway in the metabolism of anti-PDAC chemotherapeutic drugs, particularly its biological interpretation, requires a further investigation.
Integrative systems and functional analyses reveal a role of dopaminergic signaling in myelin pathogenesis
Authors: Ding Sujun , Gu Yun , Cai Yunyun , Cai Meijuan , Yang Tuo , Bao Shuangxi , Shen Weixing , Ni Xuejun , Chen Gang , Xing Lingyan
Published: March 2020

Background

Myelin sheaths surrounding axons are critical for electrical signal transmission in the central nervous system (CNS). Diseases with myelin defects such as multiple sclerosis (MS) are devastating neurological conditions for which few effective treatments are available. Dysfunction of the dopaminergic system has been observed in multiple neurological disorders. Its role in myelin pathogenesis, however, is unclear.

Methods

This work used a combination of literature curation, bioinformatics, pharmacological and genetic manipulation, as well as confocal imaging techniques. Literature search was used to establish a complete set of genes which is associated with MS in humans. Bioinformatics analyses include pathway enrichment and crosstalk analyses with human genetic association studies as well as gene set enrichment and causal relationship analyses with transcriptome data. Pharmacological and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) genetic manipulation were applied to inhibit the dopaminergic signaling in zebrafish. Imaging techniques were used to visualize myelin formation in vivo.

Results

Systematic analysis of human genetic association studies revealed that the dopaminergic synapse signaling pathway is enriched in candidate gene sets. Transcriptome analysis confirmed that expression of multiple dopaminergic gene sets was significantly altered in patients with MS. Pathway crosstalk analysis and gene set causal relationship analysis reveal that the dopaminergic synapse signaling pathway interacts with or is associated with other critical pathways involved in MS. We also found that disruption of the dopaminergic system leads to myelin deficiency in zebrafish.

Conclusions

Dopaminergic signaling may be involved in myelin pathogenesis. This study may offer a novel molecular mechanism of demyelination in the nervous system.
A high throughput method for quantifying number and size distribution of Arabidopsis seeds using large particle flow cytometry
Authors: Morales Alejandro , Teapal J. , Ammerlaan J. M. H. , Yin X. , Evers J. B. , Anten N. P. R. , Sasidharan R. , van Zanten M.
Published: March 2020

Background

Seed size and number are important plant traits from an ecological and horticultural/agronomic perspective. However, in small-seeded species such as Arabidopsis thaliana, research on seed size and number is limited by the absence of suitable high throughput phenotyping methods.

Results

We report on the development of a high throughput method for counting seeds and measuring individual seed sizes. The method uses a large-particle flow cytometer to count individual seeds and sort them according to size, allowing an average of 12,000 seeds/hour to be processed. To achieve this high throughput, post harvested seeds are first separated from remaining plant material (dust and chaff) using a rapid sedimentation-based method. Then, classification algorithms are used to refine the separation process in silico. Accurate identification of all seeds in the samples was achieved, with relative errors below 2%.

Conclusion

The tests performed reveal that there is no single classification algorithm that performs best for all samples, so the recommended strategy is to train and use multiple algorithms and use the median predictions of seed size and number across all algorithms. To facilitate the use of this method, an R package (SeedSorter) that implements the methodology has been developed and made freely available. The method was validated with seed samples from several natural accessions of Arabidopsis thaliana, but our analysis pipeline is applicable to any species with seed sizes smaller than 1.5 mm.
Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway
Authors: Li Xin-Xing , Zheng Xiaoting , Liu Zhenjie , Xu Qiongming , Tang Hongzhen , Feng Jianfang , Yang Shilin , Vong Chi Teng , Gao Hongwei , Wang Yitao
Published: March 2020

Background

Cryptotanshinone (CPT), as a major component of Salvia miltiorrhiza Bunge (Danshen), displays many pharmacological activities including anti-inflammatory effects. However, the exact cellular and molecular mechanisms of the anti-inflammatory activities of CPT remain to be elucidated. The present study was aimed to clarify its mechanisms on lipopolysaccharide (LPS)-induced inflammatory responses in mouse macrophages, RAW264.7 cells.

Methods

In the current study, the anti-inflammatory properties of CPT were evaluated using LPS-stimulated RAW264.7 cell model. MTT assay was used to determine the viability of RAW264.7 cells. The anti-inflammatory effects of CPT were measured based on the detection of nitric oxide (NO) production (Griess and flow cytometry assay), and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release (ELISA). Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzyme expressions were also determined by western blotting. Besides, by using flow cytometry, we also evaluated the effect of CPT on LPS-induced calcium influx. Finally, the underlying anti-inflammatory mechanisms of CPT were investigated using western blotting to assess the protein levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphatidylinositol 3-kinase (PI3K)/AKT, nuclear factor erythroid 2 related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and nuclear factor-kappa B (NF-κB) pathways.

Results

Our data showed that CPT inhibited LPS-induced pro-inflammatory cytokine release like IL-6, and TNF-α, as well as NO production. It displayed a significant inhibitory effect on the protein expressions such as iNOS, COX-2, NF-κB pathway like inhibitor of kappa B kinase (IKK)α/β, inhibitor of kappa B (IκB)-α and NF-κB/p65, PI3K/AKT pathway like PI3K and AKT, and MAPK pathway like c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, and p38, in LPS-stimulated RAW264.7 macrophages. Moreover, the immunofluorescence results indicated that CPT suppressed NF-κB/p65 translocation from the cytoplasm into the nucleus. Further investigations showed that CPT treatment increased NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) expressions together with its upstream mediator, Nrf2. In addition, CPT inhibited LPS-induced toll-like receptor 4 (TLR4) and MyD88 expressions in RAW264.7 macrophages.

Conclusions

Collectively, we suggested that CPT exerted significant anti-inflammatory effects via modulating TLR4-MyD88/PI3K/Nrf2 and TLR4-MyD88/NF-κB/MAPK pathways.
Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock
Authors: Stahl Klaus , Schmidt Julius J. , Seeliger Benjamin , Schmidt Bernhard M. W. , Welte Tobias , Haller Hermann , Hoeper Marius M. , Budde Ulrich , Bode Christian , David Sascha
Published: March 2020

Background

A dysbalanced coagulation system is part of the pathological host response to infection in sepsis. Activation of pro-coagulant pathways and attenuation of anti-coagulant activity ultimately lead to microvascular stasis and consequent organ failure. No treatment approaches specifically targeting this axis are available. We explored the effects of therapeutic plasma exchange (TPE) on microvascular coagulation dysbalance in septic shock.

Methods

We conducted a prospective single-center study enrolling 31 patients with early septic shock (onset < 12 h) requiring high doses of norepinephrine (NE > 0.4 μg/kg/min). Clinical and biochemical data, including measurement of protein C; a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13); and von Willebrand factor antigen (vWF:Ag), were obtained before and after TPE against fresh frozen plasma.

Results

Antithrombotic acting proteins such as antithrombin-III (ATIII) and protein C were markedly reduced in septic patients, but their activity increased after TPE (ATIII, 51% (41–61) vs. 63% (48–70), p = 0.029; protein C, 47% (38–60) vs. 62% (54–69), p = 0.029). Median ADAMTS13 activity was increased by TPE from 27 (21–42) % before to 47 (38–62) % after TPE (p < 0.001). In contrast, vWF:Ag was elevated and could be reduced by TPE (353 (206–492) IU/dL vs. 170 (117–232) IU/dL, p < 0.001). Regression analysis yielded a correlation between ADAMTS13 activity and platelet count (p = 0.001, R2 = 0.316).

Conclusions

Septic shock was associated with activation of pro-coagulant pathways and simultaneous depletion of anti-coagulant factors. TPE partially attenuated this dysbalance by removing pro- and by replacing anti-coagulant factors.

Trial registration

ClinicalTrials.gov, NCT03065751. Retrospectively registered on 28 February 2017.