bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progression of planovalgus deformity in patients with cerebral palsy
Authors: Min Jae Jung , Kwon Soon-Sun , Sung Ki Hyuk , Lee Kyoung Min , Chung Chin Youb , Park Moon Seok 
Published: March 2020

Abstract
Background
Analyzing radiographic changes of pes planovalgus(PV) deformity of cerebral palsy(CP) patients according to age and influencing factors.

Methods
CP patients with PV deformity younger than 18 years old who had undergone more than a year of follow-up with at least two standing foot radiographs were included. Anteroposterior and lateral talo-first metatarsal(talo-1stMT), talo-second metatarsal(talo-2ndMT), and hallux valgus(HV) angles were measured on the radiographs. The rate of progression was adjusted by multiple factors using the linear mixed model, with the Gross Motor Function Classification System(GMFCS) level as the fixed effect and age and each subject as random effects.

Results
Overall, 194 patients were enrolled in this study, and 1272 standing foot radiographs were evaluated. The AP talo-2ndMT angle progressed by 0.59° (p < 0.0001) and 0.64° (p = 0.0007) in GMFCS level II and III patients, respectively; however, there was no significant change in GMFCS level I patients (p = 0.3269). HV was significantly affected by age in all three GMFCS groups; it increased by 0.48° (p < 0.0001), 0.66° (p < 0.0001), and 1.19° (p < 0.0001) for levels I, II, and III, respectively. The lateral talo-1stMT angle showed improvements in GMFCS level I and II patients (0.43°, p < 0.0001, and 0.61°, p < 0.0001, respectively). In GMFCS level III patients, there was no significant improvement in the lateral talo-1stMT angle (p = 0.0535).

Conclusions
The GMFCS level was the single most important factor influencing the progression of radiographic indices in PV deformity in CP. The AP talo-1stMT and talo-2ndMT angles progressed in patients with GMFCS levels II and III. Physicians should take this result into consideration when planning the timing of the surgery.

Level of evidence
Prognostic Level IV.
The collaborative learning development exercise (CLeD-EX): an educational instrument to promote key collaborative learning behaviours in medical students
Authors: Pervaz Iqbal Maha , Velan Gary M. , O’Sullivan Anthony J. , Balasooriya Chinthaka 
Published: March 2020

AbstractBackgroundModern clinical practice increasingly relies on collaborative and team-based approaches to care. Regulatory bodies in medical education emphasise the need to develop collaboration and teamwork competencies and highlight the need to do so from an early stage of medical training. In undergraduate medical education, the focus is usually on collaborative learning, associated with feedback and reflection on this learning This article describes a novel educational instrument, the Collaborative Learning Development Exercise (CLeD-EX), which aims to foster the development of key collaborative learning competencies in medical students. In this article we report on the effectiveness, feasibility and educational impact of the CLeD-EX.MethodsIn this study, the “educational design research” framework was used to develop, implement and evaluate the CLeD-EX. This involved adopting a systematic approach towards designing a creative and innovative instrument which would help solve a real-world challenge in developing collaborative learning skills. The systematic approach involved a qualitative exploration of key collaborative learning behaviours which are influential in effective collaborative learning contexts. The identified competencies were employed in the design of the CLeD-EX. The design of the CLeD-EX included features to facilitate structured feedback by tutors to students, complemented by self-evaluation and reflection. The CLeD-EX was field-tested with volunteer junior medical students, using a controlled pre-test post-test design. Analysis of the completed CLeD-EX forms, self-perception surveys (i.e. pre-test and post-test surveys) and analyses of reflective reports were used to explore the educational impact of CLeD-EX, as well as its utility and practicality.ResultsAfter using the CLeD-EX, students showed a significant improvement in critical thinking and group process as measured by a previously validated instrument. Both students and tutors recognised CLeD-EX as an effective instrument, especially as a structured basis for giving and receiving feedback and for completing the feedback loop. CLeD-EX was also found to be feasible, practical and focused, while promoting learning and effective interactions in small group learning.ConclusionThe findings of this study support the introduction of an effective and feasible educational instrument such as the CLeD-EX, to facilitate the development of students’ skills in collaborative learning.
Design and clinical validation of a software program for automated measurement of mammographic breast density
Authors: Araújo Adriano L. C. , Soares Heliana B. , Carvalho Daniel F. , Mendonça Roberto M. , Oliveira Antonio G. 
Published: March 2020

Abstract
Background
Mammographic breast density is an important predictor of breast cancer, but its measurement has limitations related to subjectivity of visual evaluation or to difficult access for automatic volumetric measurement methods. Herein, we describe the design and clinical validation of Aguida, a software program for automated quantification of breast density from flat mammography images.

Materials and methods
The software program was developed in MatLab. After image segmentation separating the background from the breast image, the operator positions a cursor defining a region of interest on the pectoralis major muscle from the mediolateral oblique view. Then, in the craniocaudal view, the threshold for separation of the dense tissue is based on the optical density of the pectoral muscle, and the proportion of dense tissue is calculated by the program. Mammograms obtained from 2 different occasions in 291 women were used for clinical evaluation.

Results
The intraclass correlation coefficient (ICC) between breast density measurements by the software and by a radiologist was 0.96, with a bias of only 0.67 percentage points and a 95% limit of agreement of 13.5 percentage points; the ICC was 0.94 in the interobserver reliability assessment by two radiologists with different experience; and the ICC was 0.98 in the intraobserver reliability assessment. The distribution among the density classes was close to the values obtained with the volumetric software.

Conclusions
Measurement of breast density with the Aguida program from flat mammography images showed high agreement with the visual determination by radiologists, and high inter- and intra-observer reliability.
Spatio-temporal variations of licensed doctor distribution in China: measuring and mapping disparities
Authors: Zhu Bin , Hsieh Chih-Wei , Mao Ying 
Published: March 2020

Abstract
Background
The licensed doctor misdistribution is one of the major challenges faced by China. However, this subject remains underexplored as spatial distribution characteristics (such as spatial clustering patterns) have not been fully mapped out by existing studies. To fill the void, this study aims to explore the spatio-temporal dynamics and spatial clustering patterns of different subtypes of licensed doctors (i.e., clinicians, traditional Chinese medicine doctors, dentists, public health doctors, general practitioners) in China.

Methods
Data on the licensed doctor quantity and population during 2012–2016 was obtained from the National Health (and Family Planning) Yearbook. Functional boxplots were used to visualize and compare the temporal trends of densities of different subtypes of licensed doctors. This study adopted two complementary spatial statistics (space-time scan statistics and Moran’s I statistics) to explore the spatio-temporal dynamics and spatial clustering patterns of licensed doctor distribution in China. The former was used to explore the spatial variations in the temporal trends of licensed doctor density during 2012–2016, and the latter was adopted to explore the spatial changing patterns of licensed doctor distribution during the research period.

Results
The results show that the densities of almost all subtypes of licensed doctors displayed upward trends during 2012–2016, though some provincial units were left behind. Besides, spatial distribution characteristics varied across different subtypes of licensed doctors, with the low-low cluster area of general practitioners being the largest.

Conclusions
The misdistribution of licensed doctors is a global problem and China is no exception. In order to achieve a balanced distribution of licensed doctors, the government is suggested to introduce a series of measures, such as deliberative policy design and effective human resource management initiatives to educate, recruit, and retain licensed doctors and prevent a brain drain of licensed doctors from disadvantaged units.
The effectiveness of frequent antibiotic use in reducing the risk of infection-related hospital admissions: results from two large population-based cohorts
Authors: van Staa Tjeerd Pieter , Palin Victoria , Li Yan , Welfare William , Felton Timothy W. , Dark Paul , Ashcroft Darren M. 
Published: March 2020

Abstract
Background
Previous research reported that individuals prescribed antibiotics frequently develop antimicrobial resistance. The objective of this study was to evaluate whether frequent antibiotic use is associated with reduced hospital admissions for infection-related complications.

Methods
Population-based cohort study analysing electronic health records from primary care linked to hospital admission records. The study population included patients prescribed a systemic antibiotic, recent record of selected infections and no history of chronic obstructive pulmonary disease. Propensity-matched cohorts were identified based on quintiles of prior antibiotic use in 3 years before.

Results
A total of 1.8 million patients were included. Repeated antibiotic use was frequent. The highest rates of hospital admissions for infection-related complications were observed shortly after antibiotic start in all prior exposure quintiles. For patients with limited prior antibiotic use, rates then dropped quickly and substantially. In contrast, reductions over time were substantially less in patients with frequent prior antibiotic use, with rates remaining elevated over the following 6 months. In patients without comorbidity comparing the highest to lowest prior exposure quintiles in the Clinical Practice Research Databank, the IRRs were 1.18 [95% CI 0.90–1.55] in the first 3 days after prescription, 1.44 [95% CI 1.14–1.81] in the days 4–30 after and 3.22 [95% CI 2.29–4.53] in the 3–6 months after.

Conclusions
Repeated courses of antibiotics, although common practice, may have limited benefit and indicator of adverse outcomes. A potential mechanism is that antibiotics may cause dysbiosis (perturbations of intestinal microbiota), contributing to colonization with resistant bacteria. Antibiotics should be used judiciously and only periodically unless indicated. Antimicrobial stewardship should include activities focusing on the substantive number of patients who repeatedly but intermittently get antibiotics.
Applied mathematical modelling to inform national malaria policies, strategies and operations in Tanzania
Authors: Runge Manuela , Molteni Fabrizio , Mandike Renata , Snow Robert W. , Lengeler Christian , Mohamed Ally , Pothin Emilie 
Published: March 2020

Abstract
Background
More than ever, it is crucial to make the best use of existing country data, and analytical tools for developing malaria control strategies as the heterogeneity in malaria risk within countries is increasing, and the available malaria control tools are expanding while large funding gaps exist. Global and local policymakers, as well as funders, increasingly recognize the value of mathematical modelling as a strategic tool to support decision making. This case study article describes the long-term use of modelling in close collaboration with the National Malaria Control Programme (NMCP) in Tanzania, the challenges encountered and lessons learned.

Case description
In Tanzania, a recent rebound in prevalence led to the revision of the national malaria strategic plan with interventions targeted to the malaria risk at the sub-regional level. As part of the revision, a mathematical malaria modelling framework for setting specific predictions was developed and used between 2016 and 2019 to (1) reproduce setting specific historical malaria trends, and (2) to simulate in silico the impact of future interventions. Throughout the project, multiple stakeholder workshops were attended and the use of mathematical modelling interactively discussed.

Evaluation
In Tanzania, the model application created an interdisciplinary and multisectoral dialogue platform between modellers, NMCP and partners and contributed to the revision of the national malaria strategic plan by simulating strategies suggested by the NMCP. The uptake of the modelling outputs and sustained interest by the NMCP were critically associated with following factors: (1) effective sensitization to the NMCP, (2) regular and intense communication, (3) invitation for the modellers to participate in the strategic plan process, and (4) model application tailored to the local context.

Conclusion
Empirical data analysis and its use for strategic thinking remain the cornerstone for evidence-based decision-making. Mathematical impact modelling can support the process both by unifying all stakeholders in one strategic process and by adding new key evidence required for optimized decision-making. However, without a long-standing partnership, it will be much more challenging to sensibilize programmes to the usefulness and sustained use of modelling and local resources within the programme or collaborating research institutions need to be mobilized.
Bayesian spatiotemporal modeling with sliding windows to correct reporting delays for real-time dengue surveillance in Thailand
Authors: Rotejanaprasert Chawarat , Ekapirat Nattwut , Areechokchai Darin , Maude Richard J. 
Published: March 2020

Abstract
Background
The ability to produce timely and accurate estimation of dengue cases can significantly impact disease control programs. A key challenge for dengue control in Thailand is the systematic delay in reporting at different levels in the surveillance system. Efficient and reliable surveillance and notification systems are vital to monitor health outcome trends and early detection of disease outbreaks which vary in space and time.

Methods
Predicting the trend in dengue cases in real-time is a challenging task in Thailand due to a combination of factors including reporting delays. We present decision support using a spatiotemporal nowcasting model which accounts for reporting delays in a Bayesian framework with sliding windows. A case study is presented to demonstrate the proposed nowcasting method using weekly dengue surveillance data in Bangkok at district level in 2010.

Results
The overall real-time estimation accuracy was 70.69% with 59.05% and 79.59% accuracy during low and high seasons averaged across all weeks and districts. The results suggest the model was able to give a reasonable estimate of the true numbers of cases in the presence of delayed reports in the surveillance system. With sliding windows, models could also produce similar accuracy to estimation with the whole data.

Conclusions
A persistent challenge for the statistical and epidemiological communities is to transform data into evidence-based knowledge that facilitates policy making about health improvements and disease control at the individual and population levels. Improving real-time estimation of infectious disease incidence is an important technical development. The effort in this work provides a template for nowcasting in practice to inform decision making for dengue control.
PARP inhibitors in pancreatic cancer: molecular mechanisms and clinical applications
Authors: Zhu Heng , Wei Miaoyan , Xu Jin , Hua Jie , Liang Chen , Meng Qingcai , Zhang Yiyin , Liu Jiang , Zhang Bo , Yu Xianjun , Shi Si 
Published: March 2020

AbstractPancreatic cancer is a highly lethal disease with a poor prognosis, and existing therapies offer only limited effectiveness. Mutation gene sequencing has shown several gene associations that may account for its carcinogenesis, revealing a promising research direction. Poly (ADP-ribose) polymerase (PARP) inhibitors target tumor cells with a homologous recombination repair (HRR) deficiency based on the concept of synthetic lethality. The most prominent target gene is BRCA, in which mutations were first identified in breast cancer and ovarian cancer. PARP inhibitors can trap the PARP-1 protein at a single-stranded break/DNA lesion and disrupt its catalytic cycle, ultimately leading to replication fork progression and consequent double-strand breaks. For tumor cells with BRCA mutations, HRR loss would result in cell death. Pancreatic cancer has also been reported to have a strong relationship with BRCA gene mutations, which indicates that pancreatic cancer patients may benefit from PARP inhibitors. Several clinical trials are being conducted and have begun to yield results. For example, the POLO (Pancreatic Cancer Olaparib Ongoing) trial has demonstrated that the median progression-free survival was observably longer in the olaparib group than in the placebo group. However, PARP inhibitor resistance has partially precluded their use in clinical applications, and the major mechanism underlying this resistance is the restoration of HRR. Therefore, determining how to use PARP inhibitors in more clinical applications and how to avoid adverse effects, as well as prognosis and treatment response biomarkers, require additional research. This review elaborates on future prospects for the application of PARP inhibitors in pancreatic cancer.
Assessing whether ad hoc clinician-generated patient questionnaires provide psychometrically valid information
Authors: Lee Minji K. , Basford Jeffrey R. , Heinemann Allen W. , Cheville Andrea 
Published: March 2020

Abstract
Background
The provision of psychometrically valid patient reported outcomes (PROs) improves patient outcomes and reflects their quality of life. Consequently, ad hoc clinician-generated questionnaires of the past are being replaced by more rigorous instruments. This change, while beneficial, risks the loss/orphaning of decades-long information on difficult to capture/chronically ill populations. The goal of this study was to assess to the quality of data retrieved from these legacy questionnaires.

Methods
Participants included 8563 patients who generated a total of 12,626 hospital admissions over the 2004–2014 study period. Items used to screen for issues related to function, mood, symptoms, and social support among patients with chronic disease were identified in our medical center’s patient information questionnaire. Cluster and exploratory factor analyses (EFA) followed by multidimensional item response theory (MIRT) analyses were used to select items that defined factors. Scores were derived with summation and MIRT approaches; inter-factor relationships and relationships of factor scores to assigned diagnostic codes were assessed. Rasch analyses assessed the constructs’ measurement properties.

Results
Literature review and clinician interviews yielded four hypothesized constructs: psychological distress/wellbeing, symptom burden, social support, and physical function. Rasch analyses showed that, while all had good measurement properties, only one, function, separated individuals well. In exploratory factor analyses (EFA), 11 factors representing depression, respiratory symptoms, musculoskeletal pain, family support, mobility, activities of daily living, alcohol consumption, weight loss, fatigue, neurological disorders, and fear at home were identified. Based on the agreement between EFA and cluster analyses as well as Cronbach’s alpha, six domains were retained for analyses. Correlations were strong between activities of daily living and mobility (.84), and moderate between pain and mobility (.37) and psychological distress (.59) Known-group validity was supported from the relationships between factor scores and the relevant diagnostic code assignments (.12 to .20).

Conclusions and discussion
Items from ad hoc clinician-generated patient information questionnaires can be aggregated into valid factors that assess supportive care domains among chronically ill patients. However, the binary response options offered by many screening items limit their information content and consequently, as highlighted by Rasch analyses, their ability to meaningfully discriminate trait levels in these populations.
An engineering probiotic producing defensin-5 ameliorating dextran sodium sulfate-induced mice colitis via Inhibiting NF-kB pathway
Authors: Zeng Lishan , Tan Jiasheng , Xue Meng , Liu Le , Wang Mingming , Liang Liping , Deng Jun , Chen Wei , Chen Ye 
Published: March 2020

Abstract
Background
Human defensin-5 (HD-5) is a key antimicrobial peptide which plays an important role in host immune defense, while the short half-life greatly limits its clinical application. The purpose of this study was to investigate the effects of an engineering probiotic producing HD-5 on intestinal barrier and explore its underlying mechanism

Methods
We constructed the pN8148-SHD-5 vector, and transfected this plasmid into Lactococcus lactis (L. lactis) to create the recombinant NZ9000SHD-5 strain, which continuously produces mature HD-5. NZ9000SHD-5 was administrated appropriately in a dextran sodium sulfate (DSS)-induced colitis model. Alterations in the wounded intestine were analyzed by hematoxylin–eosin staining. The changes of intestinal permeability were detected by FITC-dextran permeability test, the tight junction (TJ) proteins ZO-1 and occludin and cytokines were analyzed by western blotting or enzyme linked immunosorbent assay. In Caco-2 cell monolayers, the permeability were analyzed by transepithelial electrical resistance, and the TJ proteins were detected by western blotting and immunofluorescence. In addition, NF-κB signaling pathway was investigated to further analyze the molecular mechanism of NZ9000SHD-5 treatment on inducing intestinal protection in vitro.

Results
We found oral administration with NZ9000SHD-5 significantly reduced colonic glandular structure destruction and inflammatory cell infiltration, downregulated expression of several inflammation-related molecules and preserved epithelial barrier integrity. The same protective effects were observed in in vitro experiments, and pretreatment of macrophages with NZ9000SHD-5 culture supernatants prior to LPS application significantly reduced the expression of phosphorylated nuclear transcription factor-kappa B (NF-κB) p65 and its inhibitor IκBα.

Conclusions
These results indicate the NZ9000SHD-5 can alleviate DSS-induced mucosal damage by suppressing NF-κB signaling pathway, and NZ9000SHD-5 may be a novel therapeutic means for ulcerative colitis.