bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractBackgroundNatural 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.ResultsWe 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.ConclusionsThe 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

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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundRelationships 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.MethodsThis 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.ResultsThe 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.ConclusionThe 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

AbstractIt 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

AbstractPancreatic 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

AbstractAs 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

Abstract
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.