bluuebunny/crossref_metadata_2025_split huggingface dataset:
The top 1%: quantifying the unequal distribution of malaria in Brazil
Authors: Lana Raquel , Nekkab Narimane , Siqueira Andre M. , Peterka Cassio , Marchesini Paola , Lacerda Marcus , Mueller Ivo , White Michael , Villela Daniel 
Published: February 2021

Abstract
Background
As malaria endemic countries strive towards elimination, intensified spatial heterogeneities of local transmission could undermine the effectiveness of traditional intervention policy.

Methods
The dynamic nature of large-scale and long-term malaria heterogeneity across Brazilian Amazon basin were explored by (1) exploratory analysis of Brazil’s rich clinical malaria reporting database from 2004 to 2018, and (2) adapting Gini coefficient to study the distribution of malaria cases in the region.

Results
As transmission declined, heterogeneity increased with cases clustering into smaller subpopulations across the territory. In 2004, the 1% of health units with the greatest number of cases accounted for 46% of all reported Plasmodium vivax cases, whereas in 2018 52% of P. vivax cases occurred in the top 1% of health units. Plasmodium falciparum had lower levels of transmission than P. vivax, and also had greater levels of heterogeneity with 75% of cases occurring in the top 1% of health units. Age and gender stratification of cases revealed peri-domestic and occupational exposure settings that remained relatively stable.

Conclusion
The pathway to decreasing incidence is characterized by higher proportions of cases in males, in adults, due to importation, and caused by P. vivax. Characterization of spatio-temporal heterogeneity and risk groups can aid stratification for improved malaria control towards elimination with increased heterogeneity potentially allowing for more efficient and cost-effective targeting. Although distinct epidemiological phenomena were clearly observed as malaria transmission declines, the authors argue that there is no canonical path to malaria elimination and a more targeted and dynamic surveillance will be needed if Brazil decides to adopt the elimination target.
An integrated analysis of spatial access to the three-tier healthcare delivery system in China: a case study of Hainan Island
Authors: Wang Xiuli , Seyler Barnabas C. , Han Wei , Pan Jay 
Published: February 2021

Abstract
Background
Access to healthcare is critical for the implementation of Universal Health Coverage. With the development of healthcare insurance systems around the world, spatial impedance to healthcare institutions has attracted increasing attention. However, most spatial access methodologies have been developed in Western countries, whose healthcare systems are different from those in Low- and Middle-Income Countries (LMICs).

Methods
Hainan Island was taken as an example to explore the utilization of modern spatial access techniques under China’s specialized Three-Tier Health Care Delivery System. Healthcare institutions were first classified according to the three tiers. Then shortest travel time was calculated for each institution’s tier, overlapped to identify eight types of multilevel healthcare access zones. Spatial access to doctors based on the Enhanced Two-Step Floating Catchment Area Method was also calculated.

Results
On Hainan Island, about 90% of the population lived within a 60-min service range for Tier 3 (hospital) healthcare institutions, 80% lived within 30 min of Tier 2 (health centers), and 75% lived within 15 min of Tier 1 (clinics). Based on local policy, 76.36% of the population living in 48.52% of the area were able to receive timely services at all tiers of healthcare institutions. The weighted average access to doctors was 2.31 per thousand residents, but the regional disparity was large, with 64.66% being contributed by Tier 3 healthcare institutions.

Conclusion
Spatial access to healthcare institutions on Hainan Island was generally good according to travel time and general abundance of doctors, but inequity between regions and imbalance between different healthcare institution tiers exist. Primary healthcare institutions, especially in Tier 2, should be strengthened.
Working towards universal health coverage: a qualitative study to identify strategies for improving student enrolment for the pre-service training of nurses, midwives and community health workers in Nigerian health training institutions
Authors: Okereke Ekechi , Ahonsi Babatunde 
Published: February 2021

Abstract
Background
Student enrolment processes and practices can affect the quality of pre-service training programmes. These processes and practices may have serious implications for the quality and quantity of students within health training institutions, the quality of education for prospective health workers and consequently health workforce performance. This study assessed current student enrolment processes and practices for nurses, midwives and community health workers within health training institutions in two Nigerian states, so as to identify strategies for improving student enrolment for these key cadres of frontline health workers.

Methods
This study was carried out in Bauchi and Cross-River States, which are the two Human Resources for Health (HRH) project focal states in Nigeria. Utilizing a qualitative research design, 55 in-depth interviews and 13 focus group discussions were conducted with key stakeholders including students and tutors from pre-service health training institutions as well as policy-makers and public sector decision-makers from Ministries of Health, Government Agencies and Regulatory Bodies. Study participants were purposively sampled and the qualitative data were audio-recorded, transcribed and then thematically analysed.

Results
Study participants broadly described the application process to include the purchase, completion and submission of application forms by prospective students prior to participation in entrance examinations and oral interviews. The use of ‘weeding examinations’ during the student enrolment process, especially in Bauchi state, was identified as a useful quality assurance mechanism for the pre-service training programmes of frontline health workers. Other strategies identified by stakeholders to address challenges with student enrolment include sustained advocacy to counter-cultural norms and gender stereotypes vis-à-vis certain professions, provision of scholarships for trainee frontline health workers and ultimately the development as well as effective implementation of national and state-specific policy and implementation guidelines for the student enrolment of key frontline health workers.

Conclusion
While there are challenges which currently affect student enrolment for nurses, midwives and community health workers in Nigeria, this study has proposed key strategies which if carefully considered and implemented can substantially improve the status quo. These will probably have far-reaching implications for improving health workforce performance, population health outcomes and efforts to achieve universal health coverage.
Implementation of evidence-based practice and associated factors among nurses and midwives working in Amhara Region government hospitals: a cross-sectional study
Authors: Dagne Asrat Hailu , Beshah Mekonnen Haile , Kassa Bekalu Getnet , Dagnaw Eyaya Habtie 
Published: February 2021

Abstract
Background
Implementation of evidence-based practice is crucial to enhance quality health care, professional development, and cost-effective health service. However, many factors influence the implementation of evidence-based practice. Therefore, this study aimed to assess the implementation of evidence-based practice and associated factors among nurses and midwives.

Methods
Institutional-based cross-sectional study design was conducted to assess the implementation of evidence-based practice and associated factors from February 15 to March 15, 2019, among 790 nurses and midwives. Data were entered into EpiData version 3.1 then exported to SPSS version 20 for statistical analysis. Categorical variables were presented as frequency tables. Continuous variables were presented as descriptive measures, expressed as mean and standard deviation. Cronbach’s alpha was used to measure reliability, mean, standard deviation, and inter-items correlation of the factors. Independent variables with a probability value (P-value) of less than 0.2 in the Chi-square analysis were entered in the multivariable logistic regression model. Statistically significant associated factors were identified at probability value (P-value) less than 0.05 and adjusted odds ratio with a 95% confidence interval.

Results
The mean age of participants was 28.35 (SD ± 4.5) years. This study revealed that 34.7% (95% CI 31.5–38%) of participants implemented evidence-based practice moderately or desirably. Age of participants (AOR = 5.98, CI 1.34–26.7), barriers of implementation of evidence-based practice (AOR = 4.8, CI 2.2–10.6), the attitude of participants (AOR = 5.02, CI 1.2–21.5), nursing/midwifery work index (AOR = 3.9, CI 1.4–10.87), self-efficacy of implementation of evidence-based practice skills (AOR = 12.5, CI 5.7–27.5) and knowledge of participants (AOR = 3.06, CI 1.6–5.77) were statistically significant associated factors of implementation of evidence-based practice

Concussion
Implementation of evidence-based practice of nurses and midwives was poor. Age of participants, barriers of implementation of evidence-based practice, the attitude of participants, self-efficacy of implementation of evidence-based practice skills, nursing/midwifery work index, and knowledge of participants were found to be predictors of implementation of evidence-based practice. Insufficient time and difficulty in judging the quality of research papers and reports were the most common barriers to the implementation of evidence-based practice.
Three-dimensional evaluations of preoperative planning reproducibility for the osteosynthesis of distal radius fractures
Authors: Yoshii Yuichi , Ogawa Takeshi , Shigi Atsuo , Oka Kunihiro , Murase Tsuyoshi , Ishii Tomoo 
Published: February 2021

Abstract
Background
Three-dimensional preoperative planning was applied for the osteosynthesis of distal radius fractures. The objective of this study was to evaluate the reproducibility of three-dimensional preoperative planning for the osteosynthesis of distal radius fractures with three-dimensional reference points.

Methods
Sixty-three wrists of 63 distal radius fracture patients who underwent osteosynthesis with three-dimensional preoperative planning were evaluated. After taking preoperative CT scans of the injured wrists, 3D images of the distal radius were created. Fracture reduction, implants choices, and placements simulation were performed based on the 3D images. One month after the surgery, postoperative CT images were taken. The reproducibility was evaluated with preoperative plan and postoperative 3D images. The images were compared with the three-dimensional coordinates of radial styloid process, volar and dorsal edges of sigmoid notch, and the barycentric coordinates of the three reference points. The reproducibility of the preoperative plan was evaluated by the distance of the coordinates between the plan and postoperative images for the reference points. The reproducibility of radial inclination and volar tilt on three-dimensional images were evaluated by intra-class correlation coefficient (ICC).

Results
The distances between the preoperative plan and the postoperative reduction for each reference point were (1) 2.1±1.3 mm, (2) 1.9±1.2 mm, and (3) 1.9±1.2 mm, respectively. The distance between the preoperative plan and postoperative reduction for the barycentric coordinate was 1.3±0.8 mm. ICCs were 0.54 and 0.54 for the volar tilt and radial inclination, respectively (P<0.01).

Conclusions
Three-dimensional preoperative planning for the osteosynthesis of distal radius fracture was reproducible with an error of about 2 mm for each reference point and the correlations of reduction shapes were moderate. The analysis method and reference points may be helpful to understand the accuracy of reductions for the three-dimensional preoperative planning in the osteosynthesis of distal radius fractures.

Trial registration
Registered as NCT02909647 at ClinicalTrials.gov
PDK1 is a negative regulator of axon regeneration
Authors: Kim Hyemin , Lee Jinyoung , Cho Yongcheol 
Published: February 2021

AbstractAxon regeneration in the central nervous system is inefficient. However, the neurons in the peripheral nervous system display robust regeneration after injury, indicating that axonal regeneration is differentially controlled under various conditions. To identify those molecules regulating axon regeneration, comparative analysis from dorsal root ganglion neurons at embryonic or adult stages is utilized, which reveals that PDK1 is functions as a negative regulator of axon regeneration. PDK1 is downregulated in embryonic neurons after axotomy. In contrast, sciatic nerve axotomy upregulated PDK1 at protein levels from adult mice. The knockdown of PDK1 or the chemical inhibition of PDK1 promotes axon regeneration in vitro and in vivo. Here we present PDK1 as a new player to negatively regulate axon regeneration and as a potential target in the development of therapeutic applications.
A pre-hospital risk score predicts critical illness in non-trauma patients transported by ambulance to a Dutch tertiary referral hospital
Authors: Veldhuis Lars I. , Hollmann Markus W. , Kooij Fabian O. , Ridderikhof Milan L. 
Published: February 2021

Abstract
Background
Early pre-hospital identification of critically ill patients reduces morbidity and mortality. To identify critically ill non-traumatic and non-cardiac arrest patients, a pre-hospital risk stratification tool was previously developed in the United States. The aim of this study was to investigate the accuracy of this tool in a Dutch Emergency Department.

Methods
This retrospective study included all patients of 18 years and older transported by ambulance to the Emergency Department of a tertiary referral hospital between January 1st 2017 and December 31st 2017. Documentation of pre-hospital vital parameters had to be available. The tool included a full set of vital parameters, which were categorized by predetermined thresholds.
Study outcome was the accuracy of the tool in predicting critical illness, defined as admittance to the Intensive Care Unit for delivery of vital organ support or death within 28 days. Accuracy of the risk stratification tool was measured with the Area Under the Receiver Operating Characteristics (AUROC) curve.

Results
Nearly 3000 patients were included in the study, of whom 356 patients (12.2%) developed critical illness. We observed moderate discrimination of the pre-hospital risk score with an AUROC of 0.74 (95%-CI 0.71–0.77). Using a threshold of 3 to identify critical illness, we observed a sensitivity of 45.0% (95%-CI 44.8–45.2) and a specificity of 86.0% (95%-CI 85.9–86.0).

Conclusion
These data show that this pre-hospital risk stratification tool is a moderately effective tool to predict which patients are likely to become critically ill in a Dutch non-trauma and non-cardiac arrest population.
Room for improvement: One third of Lynch syndrome patients presenting for genetic testing in a highly specialised centre in Stockholm already have cancer
Authors: Bernstedt Sophie Walton , Björk Jan , Fritzell Kaisa , Spigelman Allan D. , Björck Erik , Backman Ann-Sofie 
Published: February 2021

Abstract
Background
Lynch syndrome is caused by germline mutations in the mismatch repair genes and is characterised by a familial accumulation of colorectal and other cancers. Earlier identification of Lynch syndrome patients enables surveillance and might reduce the risk of cancer. It is important to explore whether today’s clinical care discovers patients with Lynch syndrome suitable for surveillance in time. This study aimed to describe what led to a diagnosis of Lynch syndrome in the cohort referred to the Hereditary Gastrointestinal Cancer Unit, Karolinska University Hospital, Solna, Sweden for gastrointestinal surveillance.

Methods
This was a descriptive study. Data from 1975 to 2018 were collected and compiled as a database. Age at diagnosis was calculated from the date when a pathogenic MMR gene mutation was confirmed, from the period June 1994–September 2018. Data were collected from patient protocols prospectively during patient consultations and medical records retrospectively. Criteria for inclusion were registration at the outpatient clinic and a confirmed mismatch repair gene mutation.

Results
A total of 305 patients were eligible for inclusion. Three major reasons for diagnosis were identified: 1. Predictive testing of a previously known mutation in the family (62%, mean age 37), 2. A family history of Lynch associated tumours (9%, mean age 37), 3. A diagnosis of cancer (29%, mean age 51). The proportion diagnosed due to cancer has not changed over time.

Conclusion
A high proportion of patients (29%) were identified with Lynch syndrome after they had been diagnosed with an associated cancer, which suggests that there is significant room for improvement in the diagnosis of patients with Lynch syndrome before cancer develops.
Fluorescent cystoscopy-assisted en bloc transurethral resection versus conventional transurethral resection in patients with non-muscle invasive bladder cancer: study protocol of a prospective, open-label, randomized control trial (the FLEBER study)
Authors: Miyake Makito , Nishimura Nobutaka , Inoue Takashi , Suzuki Shota , Fujii Tomomi , Owari Takuya , Hori Shunta , Nakai Yasushi , Toritsuka Michihiro , Nakagawa Hitoshi , Tsukamoto Shinji , Anai Satoshi , Torimoto Kazumasa , Yoneda Tatsuo , Tanaka Nobumichi , Fujimoto Kiyohide 
Published: February 2021

Abstract
Background
Transurethral resection of bladder tumor (TURBT) is an essential procedure both for the treatment and staging of bladder cancer, particularly non-muscle invasive bladder cancer (NMIBC). The dissemination of cancer cells during resection and the consequent seeding into the bladder mucosa is the main cause of post-TURBT intravesical recurrence. Although the tumor dissemination is inevitable during conventional TURBT (cTURBT), this drawback can be overcome by tumor resection in one piece with intact surrounding normal tissues, referred to as en bloc resection. We previously described the photodynamic diagnosis (PDD)-assisted en bloc TURBT (EBTUR) technique and its favorable outcomes. Based on our preliminary studies, this randomized controlled trial was designed to evaluate the superiority of PDD-EBTUR to PDD-cTURBT.

Methods
The FLEBER study is a single-center randomized controlled trial in NMIBC patients who require TURBT. The longest diameter of the tumor must be between 6 and 30 mm. A total of 160 eligible patients will be enrolled after screening and randomly allocated to the PDD-EBTUR (experimental) and PDD-cTURBT (control) groups in a 1:1 ratio (80 cases to 80 cases). All patients will be treated using a single, immediate postoperative intravesical chemotherapy with epirubicin. The primary endpoint of this trial is the 2-year recurrence-free survival after surgery in pathologically proven low- or intermediate-risk NMIBC. All patients will be monitored by cystoscopy and urine cytology every 3 months for 2 years. Patient data including adverse events and complications, and data from frequency volume charts, pain scales, and health-related QOL questionnaires will be collected before and after the TURBT at indicated visits.

Discussion
The goal of this trial is to determine the potential benefits of PDD-cTURBT and PDD-EBTUR followed by a single immediate postoperative intravesical chemotherapy in patients with low- or intermediate-risk NMIBC who undergo TURBT. Ultimately, our findings will lead to the development of better interventions and potentially change the standard of care.

Trial registration
This clinical trial was prospectively registered with the UMIN Clinical Trials Registry on 1 August 2020. The reference number is UMIN000041273, and the Ethics Committee of Nara Medical University Approval ID is 2702.
Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS): a double-blind randomised placebo-controlled crossover trial
Authors: Myat Aung , Redwood Simon R. , Arri Satpal , Gersh Bernard J. , Bhatt Deepak L. , Marber Michael S. 
Published: February 2021

Abstract
Background
Glucagon-like peptide-1 receptor (GLP-1R) activation may improve myocardial performance in the context of ischaemia, independent of glycaemic control, in individuals with and without type 2 diabetes mellitus.

Methods
The LIONESS trial was a single-centre randomised double-blind placebo-controlled crossover study to determine whether prolonged GLP-1R activation could improve exercise haemodynamics in chronic stable angina patients. Eligibility criteria comprised angiographic evidence of obstructive coronary artery disease (CAD) and an abnormal baseline exercise tolerance test (ETT) demonstrating > 0.1 mV of planar or downsloping ST-segment depression (STD). Those randomised to active agent started with a 1-week run-in phase of 0.6 mg liraglutide daily, an established injectable GLP-1R agonist, followed by 1 week of 1.2 mg liraglutide, after which patients performed a week 2 ETT. Patients then self-administered 1.8 mg liraglutide for a week before completing a week 3 ETT. The placebo arm received visually and temporally matched daily saline injections. Participants then crossed over to a 3-week course of saline injections interspersed with a week 5 ETT and week 6 ETT and vice versa. Co-primary endpoints were rate pressure product (RPP) at 0.1 mV STD and magnitude of STD at peak exercise.

Results
Twenty-two patients (21 without diabetes) were randomised. There was no significant difference between saline versus liraglutide in the co-primary endpoints of RPP achieved at 0.1 mV STD (saline vs. liraglutide 1.2 mg p = 0.097; saline vs. liraglutide 1.8 mg p = 0.48) or the degree of STD at peak exercise (saline vs. liraglutide 1.2 mg p = 0.68; saline vs. liraglutide 1.8 mg p = 0.57). Liraglutide did not cause symptomatic hypoglycaemia, renal dysfunction, acute pancreatitis or provoke early withdrawal from the trial. Liraglutide significantly reduced weight (baseline 88.75 ± 16.5 kg vs. after liraglutide 87.78 ± 16.9 kg; p = 0.0008) and improved the lipid profile (mean total cholesterol: at baseline 3.97 ± 0.88 vs. after liraglutide 3.56 ± 0.71 mmol/L; p < 0.0001).

Conclusion
Liraglutide did not enhance exercise tolerance or haemodynamics compared with saline placebo during serial treadmill testing in patients with established obstructive CAD. It did, however, significantly reduce weight and improve the lipid profile.
Trial Registration ClinicalTrials.gov Identifier NCT02315001. Retrospectively registered on 11th December 2014.