bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connected health for growth hormone treatment research and clinical practice: learnings from different sources of real-world evidence (RWE)—large electronically collected datasets, surveillance studies and individual patients’ cases
Authors: Boman Nea , Fernandez-Luque Luis , Koledova Ekaterina , Kause Marketta , Lapatto Risto 
Published: April 2021

Abstract
Background
A range of factors can reduce the effectiveness of treatment prescribed for the long-term management of chronic health conditions, such as growth disorders. In particular, prescription medications may not achieve the positive outcomes expected because approximately half of patients adhere poorly to the prescribed treatment regimen.

Methods
Adherence to treatment has previously been assessed using relatively unreliable subjective methods, such as patient self-reporting during clinical follow-up, or counting prescriptions filled or vials returned by patients. Here, we report on a new approach, the use of electronically recorded objective evidence of date, time, and dose taken which was obtained through a comprehensive eHealth ecosystem, based around the easypod™ electromechanical auto-injection device and web-based connect software. The benefits of this eHealth approach are also illustrated here by two case studies, selected from the Finnish cohort of the easypod™ Connect Observational Study (ECOS), a 5-year, open-label, observational study that enrolled children from 24 countries who were being treated with growth hormone (GH) via the auto-injection device.

Results
Analyses of data from 9314 records from the easypod™ connect database showed that, at each time point studied, a significantly greater proportion of female patients had high adherence (≥ 85%) than male patients (2849/3867 [74%] vs 3879/5447 [71%]; P < 0.001). Furthermore, more of the younger patients (< 10 years for girls, < 12 years for boys) were in the high adherence range (P < 0.001). However, recursive partitioning of data from ECOS identified subgroups with lower adherence to GH treatment ‒ children who performed the majority of injections themselves at an early age (~ 8 years) and teenagers starting treatment aged ≥ 14 years.

Conclusions
The data and case studies presented herein illustrate the importance of adherence to GH therapy and how good growth outcomes can be achieved by following treatment as described. They also show how the device, software, and database ecosystem can complement normal clinical follow-up by providing HCPs with reliable information about patient adherence between visits and also providing researchers with real-world evidence of adherence and growth outcomes across a large population of patients with growth disorders treated with GH via the easypod™ device.
Inflammation and its association with oxidative stress in dogs with heart failure
Authors: Nemec Svete Alenka , Verk Barbara , Čebulj-Kadunc Nina , Salobir Janez , Rezar Vida , Domanjko Petrič Aleksandra 
Published: April 2021

AbstractBackgroundInflammation and oxidative stress can contribute to the development and progression of heart failure. This study aimed to investigate the association between inflammatory and oxidative stress markers in dogs with congestive heart failure (CHF). Associations between the disease severity marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) and markers of inflammation and oxidative stress were also determined.ResultsThirty-seven dogs with cardiovascular diseases (dilated cardiomyopathy, DCM (16 dogs), myxomatous mitral valve disease, MMVD (21 dogs)) and ten healthy dogs were included in this prospective study. The patients were further divided into groups with (26) and without CHF (11). We found a significantly higher serum concentration of C-reactive protein (P = 0.012), white blood cell (P = 0.001), neutrophil (P = 0.001) and monocyte counts (P = 0.001) in patients with CHF compared to control dogs. The concentration of tumor necrosis factor-alpha (TNF-α) was significantly higher in patients with CHF compared to patients without CHF (P = 0.030). No significant difference was found in most of the measured parameters between MMVD and DCM patients, except for glutathione peroxidase (GPX) and NT-proBNP. In patients with CHF, TNF-α correlated positively with malondialdehyde (P = 0.014,r = 0.474) and negatively with GPX (P = 0.026,r = − 0.453), and interleukin-6 correlated negatively with GPX (P = 0.046,r = − 0.412). NT-proBNP correlated positively with malondialdehyde (P = 0.011,r = 0.493). In patients without CHF none of the inflammatory and oxidative stress markers correlated significantly. Furthermore, in the group of all cardiac patients, GPX activity significantly negatively correlated with NT-proBNP (P = 0.050,r = − 0.339) and several markers of inflammation, including TNF-α (P = 0.010,r = − 0.436), interleukin-6 (P = 0.026,r = − 0.382), white blood cell (P = 0.032,r = − 0.369), neutrophil (P = 0.027,r = − 0.379) and monocyte counts (P = 0.024,r = − 0.386).ConclusionInflammatory and oxidative stress markers are linked in canine CHF patients, but not in patients without CHF. These results suggest complex cross communication between the two biological pathways in advanced stages of CHF.
From malaria elimination to post‐elimination: a 10-year surveillance data study in Shanghai
Authors: Dai Simin , Zhu Min , Wu Huanyu , Zhang Yaoguang , Wang Zhenyu , Zhang Chengang , Ma Xiaojiang , Jiang Li 
Published: April 2021

Abstract
Background
The aim of this study was to investigate and analyse the characteristics of malaria in Shanghai from 2010 to 2019 and to provide suggestions for areas with a similar elimination process in China in order to prompt development of strategies and interventions in the post-elimination stage.

Methods
This was a cross-sectional study exploring the malaria characteristics during 2010–2019 in Shanghai, China. Malaria data from the Infectious Diseases Information Reporting Management System (IDIRMS) between 2010 and 2012 and data from the Parasitic Diseases Information Reporting Management System (PDIRMS) between 2013 and 2019 were combined for analysis in this study.

Results
From 2010 to 2019, a total of 436 malaria cases were reported in Shanghai. Among them, 415 (95.18%) were imported from abroad, 19 (4.36%) were domestically acquired from other provinces, 1 (0.23%) case was caused by blood transfusion, and 1 (0.23%) had a long incubation. Only Plasmodium vivax was found in domestically indigenous cases; Plasmodium falciparum accounted for the largest proportion of imported cases. Domestically acquired cases were only reported in 2010–2011 and 88% occurred in June to September; no significant seasonal difference was observed for imported cases over the 10 years. No local transmission has occurred in Shanghai since 2012. The median interval from fever onset to diagnosis was 3 days. Between 2010 and 2019, among 308 foci, 33 were classified as potential transmission and dispersed in suburb areas (Minhang, Baoshan, Jiading, Pudong, Jinshan, Songjiang, Qingpu, Fengxian, and Chongming). Only Anopheles sinensis was present and the proportion of Anopheles sinensis in different species of mosquitoes under surveillance in Shanghai decreased from 2011 to 2019.

Conclusions
Shanghai faces the challenge of malaria re-establishment caused by imported malaria in the post-elimination stage. Therefore, risk investigation and assessment should be carried out, and receptivity and susceptibility should be assessed for every point of focus. Training should be continued to strengthen facility staff capability, and multisectoral coordination and cooperation need to be conducted efficiently to maintain malaria elimination in Shanghai.
Distribution of under-5 deaths in the neonatal, postneonatal, and childhood periods: a multicountry analysis in 64 low- and middle-income countries
Authors: Li Zhihui , Karlsson Omar , Kim Rockli , Subramanian S. V. 
Published: April 2021

Abstract
Background
As under-5 mortality rates declined all over the world, the relative distribution of under-5 deaths during different periods of life changed. To provide information for policymakers to plan for multi-layer health strategies targeting child health, it is essential to quantify the distribution of under-5 deaths by age groups.

Methods
Using 245 Demographic and Health Surveys from 64 low- and middle-income countries conducted between 1986 and 2018, we compiled a database of 2,437,718 children under-5 years old with 173,493 deaths. We examined the share of deaths that occurred in the neonatal (< 1 month), postneonatal (1 month to 1 year old), and childhood (1 to 5 years old) periods to the total number of under-5 deaths at both aggregate- and country-level. We estimated the annual change in share of deaths to track the changes over time. We also assessed the association between share of deaths and Gross Domestic Product (GDP) per capita.

Results
Neonatal deaths accounted for 53.1% (95% confidence interval [CI]: 52.7, 53.4) of the total under-5 deaths. The neonatal share of deaths was lower in low-income countries at 44.0% (43.5, 44.5), and higher in lower-middle-income and upper-middle income countries at 57.2% (56.8, 57.6) and 54.7% (53.8, 55.5) respectively. There was substantial heterogeneity in share of deaths across countries; for example, the share of neonatal to total under-5 deaths ranged from 20.9% (14.1, 27.6) in Eswatini to 82.8% (73.0, 92.6) in Dominican Republic. The shares of deaths in all three periods were significantly associated with GDP per capita, but in different directions—as GDP per capita increased by 10%, the neonatal share of deaths would significantly increase by 0.78 percentage points [PPs] (0.43, 1.13), and the postneonatal and childhood shares of deaths would significantly decrease by 0.29 PPs (0.04, 0.54) and 0.49 PPs (0.24, 0.74) respectively.

Conclusions
Along with the countries’ economic development, an increasing proportion of under-5 deaths occurs in the neonatal period, suggesting a need for multi-layer health strategies with potentially heavier investment in newborn health.
Bacteriophage therapy for inhibition of multi drug‐resistant uropathogenic bacteria: a narrative review
Authors: Chegini Zahra , Khoshbayan Amin , Vesal Soheil , Moradabadi Alireza , Hashemi Ali , Shariati Aref 
Published: April 2021

AbstractMulti-Drug Resistant (MDR) uropathogenic bacteria have increased in number in recent years and the development of new treatment options for the corresponding infections has become a major challenge in the field of medicine. In this respect, recent studies have proposed bacteriophage (phage) therapy as a potential alternative against MDR Urinary Tract Infections (UTI) because the resistance mechanism of phages differs from that of antibiotics and few side effects have been reported for them. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are the most common uropathogenic bacteria against which phage therapy has been used. Phages, in addition to lysing bacterial pathogens, can prevent the formation of biofilms. Besides, by inducing or producing polysaccharide depolymerase, phages can easily penetrate into deeper layers of the biofilm and degrade it. Notably, phage therapy has shown good results in inhibiting multiple-species biofilm and this may be an efficient weapon against catheter-associated UTI. However, the narrow range of hosts limits the use of phage therapy. Therefore, the use of phage cocktail and combination therapy can form a highly attractive strategy. However, despite the positive use of these treatments, various studies have reported phage-resistant strains, indicating that phage–host interactions are more complicated and need further research. Furthermore, these investigations are limited and further clinical trials are required to make this treatment widely available for human use. This review highlights phage therapy in the context of treating UTIs and the specific considerations for this application.
Assessment of training and mentoring for DR-TB care decentralization in Tanzania
Authors: Lyakurwa Dennis , Lyimo Johnson , Mulder Christiaan , Pelzer Puck T. , Koppelaar Inge , Heus Marleen 
Published: April 2021

Abstract
Introduction
Drug-resistant TB (DR-TB) care shifted from centralized to decentralized care in Tanzania in 2015. This study explored whether DR-TB training and mentoring supported healthcare workers’ (HCWs) DR-TB care performance.

Methods
This mixed study assessed HCWs’ DR-TB care knowledge, the training quality, and the mentoring around 454 HCWs who were trained across 55 DR-TB sites between January 2016 and December 2017. Pre- and post-training tests, end-of-training evaluation, supervisor’s interviews, DR-TB team self-assessment and team focus group discussion were conducted among trained HCWs. Interim and final treatment results of the national central site and the decentralized sites were compared.

Results
HCW’s knowledge increased for 15–20% between pre-training and post-training. HCWs and supervisors perceived mentoring as most appropriate to further develop their DR-TB competencies. Culture negativity after 6 months of treatment was similar for the decentralized sites compared to the national central site, 81% vs 79%, respectively, whereas decentralized sites had less loss to follow-up (0% versus 3%) and fewer deaths (3% versus 12%). Delays in laboratory results, stigma, and HCWs shortage were reported the main challenges of decentralized care.

Conclusions
Training and mentoring to provide DR-TB care at decentralized sites in Tanzania improved HCWs’ knowledge and skills in DR-TB care and supported observed good interim and final patient treatment outcomes despite health system challenges.
Cost-effectiveness and value of information analysis of multiple frequency bioimpedance devices for fluid management in people with chronic kidney disease having dialysis
Authors: Jacobsen Elisabet , Cruickshank Moira , Cooper David , Marks Angharad , Brazzelli Miriam , Scotland Graham 
Published: April 2021

Abstract
Background
Among people with chronic kidney disease (CKD) on dialysis, sub-optimal fluid management has been linked with hospitalisation, cardiovascular complications and death. This study assessed the cost-effectiveness using multiple-frequency bioimpedance guided fluid management versus standard fluid management based on clinical judgment.

Methods
A Markov model was developed to compare expected costs, outcomes and quality adjusted life years of the alternative management strategies. The relative effectiveness of the bioimpedance guided approach was informed by a systematic review of clinical trials, and focussed reviews were conducted to identify baseline event rates, costs and health state utility values for application in the model. The model was analysed probabilistically and a value of information (VOI) analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base.

Results
For the base-case analysis, the incremental cost-effectiveness ratio (ICER) for bioimpedance guided fluid management versus standard management was £16,536 per QALY gained. There was a 59% chance of the ICER being below £20,000 per QALY. Form the VOI analysis, the theoretical upper bound on the value of further research was £53 million. The value of further research was highest for parameters relating to the relative effectiveness of bioimpedance guided management on final health outcomes.

Conclusions
Multiple frequency bioimpedance testing may offer a cost-effective approach to improve fluid management in patients with CKD on dialysis, but further research would be of value to reduce the current uncertainties.
A detailed mapping of the food industry in the European single market: similarities and differences in market structure across countries and sectors
Authors: Van Dam Iris , Wood Benjamin , Sacks Gary , Allais Olivier , Vandevijvere Stefanie 
Published: April 2021

Abstract
Background
Food environments are influenced by food industries (packaged food and non-alcoholic beverage manufacturers; supermarkets and quick service restaurants). An important source of this influence is the significant market power held by a limited number of food companies. Market structure analysis, as part of a broader market power research agenda, has received limited attention from the public health community. The aim of this study was to analyse similarities and differences in market structure across countries and industries in the European Single Market.

Methods
The companies with the largest market share at the national level for each industry were identified from Euromonitor sales data in 2017/18. The market structure was assessed by the following metrics: the number of global brand owners with ≥1% market share per country, the number of companies unique for one European Single Market member state, the most sold packaged food and non-alcoholic beverage categories, the number of quick-service restaurants and supermarkets per 1000 inhabitants and market concentration by means of the Herfindahl-Hirschman Index (HHI) and the four firm concentration ratio (CR4). CR4-values > 40% and HHI-values > 2000 indicate concentrated markets with limited competition.

Results
The leading packaged food and non-alcoholic beverage manufacturers and the most sold food and beverage product categories were similar across countries in Europe. The observed levels of concentration were however different. Average CR4-values ranged from 21 to 72% among packaged food product markets and 60 to 76% for non-alcoholic beverage product markets. Average CR4-values for quick service restaurants and supermarkets were 50 and 60%, respectively. Across European countries the same leading quick-service restaurants were identified, while this was not the case for supermarkets.

Conclusions
This study forms an important basis to understand key aspects of market structure of the European food industry, observing clear differences between food industries and European Single Market member states. This has potential implications for the implementation of food environment policies at different levels of jurisdiction.
Interleukin-1 blockade with RPH-104 in patients with acute ST-elevation myocardial infarction: study design and rationale
Authors: Samsonov M. , Bogin V. , Van Tassell B. W. , Abbate A. 
Published: April 2021

Abstract
Background
Myocardial injury of ST-segment elevation myocardial infarction (STEMI) initiates an intense inflammatory response that contributes to further damage and is a predictor of increased risk of death or heart failure (HF). Interleukin-1 (IL-1) is a key mediator of local and systemic inflammatory response to myocardial damage. We postulate that the use of the drug RPH-104, which selectively binds and inactivates both α and β isoforms of IL-1 will lead to a decrease in the severity of the inflammatory response which will be reflected by decrease in the concentration of hsCRP, as well as the rate of fatal outcomes, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP) and changes in structural and functional echocardiographic parameters.

Methods
This is a double blind, randomized, placebo-controlled study in which 102 patients with STEMI will receive a single administration of RPH-104 80 mg, RPH-104 160 mg or placebo (1:1:1). The primary endpoint will be hsCRP area under curve (AUC) from day 1 until day 14. Secondary endpoints will include hsCRP AUC from day 1 until day 28, rate of fatal outcomes, hospitalizations due to HF and other cardiac and non-cardiac reasons during 12-month follow-up period, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP, NT-pro-BNP), changes in structural and functional echocardiographic parameters during 12-month follow-up period compared to baseline. The study started in October 2020 and is anticipated to end in 2Q 2022.
Trial registration: ClinicalTrials.gov, NCT04463251. Registered on July 9, 2020
Biotransformation of rare earth oxide nanoparticles eliciting microbiota imbalance
Authors: Zheng Huizhen , Gu Zonglin , Pan Yanxia , Chen Jie , Xie Qianqian , Xu Shujuan , Gao Meng , Cai Xiaoming , Liu Shengtang , Wang Weili , Li Wei , Liu Xi , Yang Zaixing , Zhou Ruhong , Li Ruibin 
Published: April 2021

Abstract
Background
Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications.

Results
This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G−) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G− and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G− cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G−/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G−/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively.

Conclusions
This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G− and G+ bacteria and disclosed that La2O3-induced membrane damages of G− cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.
MAEL as a diagnostic marker for the early detection of esophageal squamous cell carcinoma
Authors: Abbaszadegan Mohammad Reza , Taghehchian Negin , Aarabi Azadeh , Akbari Faride , Saburi Ehsan , Moghbeli Meysam 
Published: April 2021

Abstract
Background
Esophageal cancer is one of the most common malignancies among Iranians and is categorized as adenocarcinoma and squamous cell carcinoma. Various environmental and genetic factors are involved in this malignancy. Despite the recent advances in therapeutic modalities there is still a noticeable mortality rate among such patients which can be related to the late diagnosis. Regarding high ratio of esophageal squamous cell carcinoma (ESCC) in Iran, therefore it is required to assess molecular biology of ESCC to introduce novel diagnostic markers. In present study we assessed the role of Maelstrom (MAEL) cancer testis gene in biology of ESCC among Iranian patients.

Methods
Forty-five freshly normal and tumor tissues were enrolled to evaluate the levels of MAEL mRNA expression using Real time polymerase chain reaction.

Results
MAEL under and over expressions were observed in 12 (26.7%) and 9 (20%) of patients, respectively. MAEL fold changes were ranged between -4.33 to -1.87 (mean SD: -2.90± 0.24) and 1.92 to 7.72 (mean SD: 3.97± 0.69) in under and over expressed cases, respectively. There was a significant association between stage and MAEL expression in which majority of MAEL over expressed tumors (8/9, 88.9%) were in stage I/II (p<0.001). There was also a significant correlation between MAEL expression and depth of invasion in which tumor with T1/2 had higher levels of MAEL expression compared with T3/4 tumors (p=0.017). Moreover, there were significant correlations between MAEL expression, tumor size (p=0.028), and grade (p=0.003) among male patients.

Conclusions
Our data showed that the MAEL was mainly involved in primary stages of tumor progression and it has a declining expression levels toward the advanced stages and higher depth of tumor invasions. Therefore, MAEL can be efficiently introduced as an early detection marker among Iranian ESCC patients.