bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative analysis of the diagnostic performances of four clinical probability models for acute pulmonary embolism in a sub-Saharan African population: a cross-sectional study
Authors: Esiéné Agnès , Tochie Joel Noutakdie , Metogo Junette Arlette Mbengono , Etoundi Paul Owono , Minkande Jacqueline Ze
Published: December 2019

Background

The diagnosis of acute pulmonary embolism (PE) is one of the most challenging in emergency settings where prompt and accurate decisions need to be taken for life-saving purposes. Here, the assessment of the clinical probability of PE is a paramount step in its diagnosis. Although clinical probability models (CPM) for PE are routinely used in emergency departments (EDs) of low-resource settings, few studies have cited their diagnostic performances in sub-Saharan Africa (SSA). We aimed to comparatively assess the accuracy of four CPM in the diagnosis of acute PE in sub-Saharan Africans.

Methods

We carried out a cross-sectional study to compare the sensitivity, specificity, positive and negative predictive values and accuracy of four CPM namely; the Wells, simplified Wells, revised Geneva and the simplified revised Geneva (SRG) Scores to computed tomography pulmonary angiography (CTPA) in all adults patients with suspected PE admitted to the EDs of the Gynaeco-obstetric and Paediatric Hospital of Yaoundé and the Yaoundé Central Hospital in Cameroon between January 1, 2017 and April 30, 2018.

Results

In total, we enrolled 30 patients with clinical suspicion of acute PE. PE was confirmed on CTPA in 16 (53.3%) cases. Their mean age was 53.7 ± 15.5 years and 36.7% were males. All four scores had a diagnostic performance superior to 50% in all criteria assessed. The simplified Wells score had the highest sensitivity (62.5%) followed by the Wells score (56.3%). The SRG score had the highest specificity (71.4%). The score with highest PPV was the SRG score (66.7%) and that with the highest NPV was the Wells score (56.3%). Overall the models with the highest accuracies were the Wells and SRG scores (60% for each).

Conclusion

All CPM had a suboptimal diagnostic performance, perhaps highlighting the need of a more optimal CPM for acute PE in SSA. However, the Wells and the SRG scores appeared to be most accurate than the other two scores in the ED. Hence, both or either of them may be used in first intention to predict PE and guide which ED patients should undergo further investigations in an emergency SSA setting.
Impact of first metatarsal shortening on forefoot loading pattern: a finite element model study
Authors: Geng Xiang , Shi Jiaqi , Chen Wenming , Ma Xin , Wang Xu , Zhang Chao , Chen Li
Published: December 2019

Backgrounds

There has long been a consensus that shortening of the first metatarsal during hallux valgus reconstruction could lead to postoperative transfer metatarsalgia. However, appropriate shortening is sometimes beneficial for correcting severe deformities or relieving stiff joints. This study is to investigate, from the biomechanical perspective, whether and how much shortening of the first metatarsal could be allowed.

Methods

A finite element model of the human foot simulating the push-off phase of the gait was established. Progressive shortening of the first metatarsal from 2 to 8 mm at an increment of 2 mm were sequentially applied to the model, and the corresponding changes in forefoot loading pattern during push-off phase, especially the loading ratio at the central rays, was calculated. The effect of depressing the first metatarsal head was also investigated.

Results

With increasing shortening level of the first metatarsal, the plantar pressure of the first ray decreased, while that of the lateral rays continued to rise. When the shortening reaches 6 mm, the load ratio of the central rays exceeds a critical threshold of 55%, which was considered risky; but it could still be manipulated to normal if the distal end of the first metatarsal displaced to the plantar side by 3 mm.

Conclusions

During the first metatarsal osteotomy, a maximum of 6 mm shortening length is considered to be within the safe range. Whenever a higher level of shortening is necessary, pushing down the distal metatarsal segment could be a compensatory procedure to maintain normal plantar force distributions.
Physical and psychosocial work environmental risk factors of low-back pain: protocol for a 1 year prospective cohort study
Authors: Bláfoss Rúni , Aagaard Per , Andersen Lars Louis
Published: December 2019

Background

Musculoskeletal disorders, and in particular low-back pain (LBP), are common among blue collar workers. In the work environment, both physical- and psychosocial risk factors exist. Working in warehouses in Denmark involve large quantities of occupational lifting, high work pace and a low degree of influence at work. This study investigates both acute and long-term associations between physical- and psychosocial work environmental factors and risk of LBP in warehouse workers. The specific study aims are to investigate 1) exposure-response associations between quantity of occupational lifting and short-term (day-to-day) changes in LBP, 2) the influence of accumulated workdays and rest days during a working week on LBP, 3) long-term association between occupational lifting exposure and LBP when assessed over 1 year, and 4) the role of psychological and social factors on the above associations.

Methods

The present study is designed as a 1-year prospective cohort study that will examine full-time warehouse workers from up to five retail chains in Denmark. Study aims 1 and 2 will be addressed using objective data based on company records with information on weight of all the goods handled by each warehouse worker during every single workday for 3 weeks. During this period, each worker will reply to text messages received before and after every workday (also on days off work) in which study participants will score their pain in the low back, bodily fatigue and perceived mental stress (scale 0–10). Long-term pain development is assessed using questionnaire surveys before and after 1 year. Further, pressure pain threshold (PPT) will be measured for selected trunk extensor muscles in approximately 50 workers using algometry along with measurements of maximal trunk extensor strength. Associations are modelled using linear mixed models with repeated measures between variables and LBP controlled for relevant confounders.

Discussion

This study provides knowledge about the acute and long-term associations between physical- and psychosocial work environmental factors and LBP. The obtained data will have the potential to provide recommendations on improved design of the working week to minimize the risk of LBP among warehouse workers, and may potentially enable to identify a reasonable maximum lifting threshold per day (ton lifted/day).
Anterior Cervical Discectomy and Fusion combined with thyroid gland surgery, a tailored case and literature review
Authors: Themistoklis Konstantinos M. , Korfias Stefanos I. , Papasilekas Themistoklis I. , Boviatsis Konstantinos A. , Kokkoros Agis G. , Spartalis Eleftherios D. , Mimidis Georgios P. , Sakas Damianos E.
Published: December 2019

Background

Nowadays, Anterior Cervical Discectomy and Fusion (ACDF) is considered a routine procedure. However, unexpected difficulties do occasionally arise, especially when anterior neck pathologies or anatomical variations are encountered. In such cases, proactive thinking will allow surgeons to tailor appropriately their approach and eliminate surgical risks.

Case presentation

We present the case of a 50-year-old male patient suffering from left upper limb radiculopathy that underwent a C7-T1 ACDF combined with a hemithyroidectomy. Excision of the right thyroid lobe was offered to the patient because of a goiter found during the preoperative work-up. Furthermore, the hemithyroidectomy provided a wide surgical field so the ACDF performed without excreting excessive traction to the adjacent neck structures.

Conclusions

The patient had an uncomplicated post-operative. To our knowledge this is the first report of a planned hemithyroidectomy being carried out as the first step towards an ACDF procedure.
The effects of cement fixation on survival in elderly patients with hip hemiarthroplasty: a nationwide cohort study
Authors: Tsai Ming-Che , Ng Yee-Yung , Chen Wei-Ming , Tsai Shang-Wen , Wu Shiao-Chi
Published: December 2019

Background

Hip hemiarthroplasty (HHA) is a common treatment for hip fractures in the elderly population. Because of the fatal effects of bone cement implantation syndrome, the safety of cement utilization to enhance implant firmness in the femur is controversial. The aim of this study was to investigate the postoperative survival of elderly patients receiving HHA with and without cement fixation.

Methods

Claim data from the National Health Insurance Database and the National Register of Deaths Database were used for analysis in this retrospective cohort study. From 2008 to 2014, 25,862 patients aged 80 years or older treated with hip hemiarthroplasty were included in the analysis. A Cox proportional risk model was used to analyse the effects of cement utilization on postoperative mortality.

Results

The cemented group had a significantly higher mortality risk than the non-cemented group within 7, 30, 180 days and 1 year after the operation. The effect of bone cement on postoperative mortality was significantly stronger within 7 days than within 30, 180 days and 1 year. In addition, the male gender, age > 85 years and higher score on the Charlson Comorbidity Index were also risk factors for mortality (p < 0.05). Patients who received HHA in lower-volume hospitals had higher mortality rates within 180 days and 1 year than those in higher-volume hospitals. Compared with patients who were operated on by high-volume surgeons, those who received surgery performed by lower-volume surgeons were more likely to die within 30 days (aHR = 1.22), 180 days (aHR = 1.16) and 1 year (aHR = 1.19), respectively.

Conclusions

The postoperative mortality rate of elderly patients undergoing HHA was significantly higher in the cemented group than in the non-cemented group.
Assessing attitudes towards medical assisted dying in Canadian family medicine residents: a cross-sectional study
Authors: Wong Aaron , Hsu Amy T. , Tanuseputro Peter
Published: December 2019

Background

Medical Assistance in Dying (MAID) in Canada came into effect in 2016 with the passing of Bill C-14. As patient interest and requests for MAID continue to evolve in Canada, it is important to understand the attitudes of future providers and the factors that may influence their participation. Attitudes towards physician hastened death (PHD) in general and the specific provision of MAID (e.g., causing death by lethal prescription or injection) are unknown among Canadian residents. This study examined residents’ attitudes towards PHD and MAID, and identified factors (e.g., demographics, clinical exposure to death and dying) that may influence their decision to participate in PHD and provide MAID.

Methods

A cross-sectional survey was adapted from prior established surveys on MAID to reflect the Canadian setting. All Canadian family medicine programs were invited to participate. The survey was distributed between December 2016 and April 2017. Analysis of the results included descriptive statistics to characterize the survey participants and multivariable logistic regressions to identify factors that may influence residents’ attitudes towards PHD and MAID.

Results

Overall, 247 residents from 6 family medicine training programs in Canada participated (response rate of 27%). While residents were most willing to participate in treatment withdrawal (52%), active participation in PHD (41%) and MAID by prescription of a lethal drug (31%) and lethal injection (24%) were less acceptable. Logistic regressions identified religion as a consistent and significant factor impacting residents’ willingness to participate in PHD and MAID. Residents who were not strictly practicing a religion were more likely to be willing to participate in PHD (OR = 17.38, p < 0.001) and MAID (lethal drug OR = 10.55, p < 0.01, lethal injection OR = 8.54, p < 0.05). Increased clinical exposure to death and dying crudely correlated with increased willingness to participate in PHD and MAID, but when examined in multivariable models, only a few activities (e.g., declaring death, completing a death certificate) had a statistically significant association. Other significant factors included the residents’ sex and location of training.

Conclusions

Residents are hesitant to provide MAID themselves, with religious faith being a major factor impacting their decision.
The impact of diabetes on multiple avoidable admissions: a cross-sectional study
Authors: Seringa Joana , Marques Ana Patrícia , Moita Bruno , Gaspar Cátia , Raposo João Filipe , Santana Rui
Published: December 2019

Background

Multiple admissions for ambulatory care sensitive conditions (ACSC) are responsible for an important proportion of health care expenditures. Diabetes is one of the conditions consensually classified as an ACSC being considered a major public health concern. The aim of this study was to analyse the impact of diabetes on the occurrence of multiple admissions for ACSC.

Methods

We analysed inpatient data of all public Portuguese NHS hospitals from 2013 to 2015 on multiple admissions for ACSC among adults aged 18 or older. Multiple ACSC users were identified if they had two or more admissions for any ACSC during the period of analysis. Two logistic regression models were computed. A baseline model where a logistic regression was performed to assess the association between multiple admissions and the presence of diabetes, adjusting for age and sex. A full model to test if diabetes had no constant association with multiple admissions by any ACSC across age groups.

Results

Among 301,334 ACSC admissions, 144,209 (47.9%) were classified as multiple admissions and from those, 59,436 had diabetes diagnosis, which corresponded to 23,692 patients. Patients with diabetes were 1.49 times (p < 0,001) more likely to be admitted multiple times for any ACSC than patients without diabetes. Younger adults with diabetes (18–39 years old) were more likely to become multiple users.

Conclusion

Diabetes increases the risk of multiple admissions for ACSC, especially in younger adults. Diabetes presence is associated with a higher resource utilization, which highlights the need for the implementation of adequate management of chronic diseases policies.
Dementia assessment and diagnostic practices of healthcare workers in rural southwestern Uganda: a cross-sectional qualitative study
Authors: Kamoga Ronald , Rukundo Godfrey Z. , Wakida Edith K. , Nakidde Gladys , Obua Celestino , Buss Stephanie S.
Published: December 2019

Background

An estimated 50 million people worldwide have Alzheimer’s disease and related dementias (ADRD), and this number is projected to increase with the growth of the aging population, with the largest growth occurring in low and middle-income countries. Diagnostic coverage for dementia is estimated to be only 5–10% in low- and middle-income countries. Timely diagnosis of ADRD could prompt early access to information, medical treatments, and support for caregivers. The aim of this study was to assess how healthcare workers in rural southwestern Uganda assess for and diagnose ADRD.

Methods

We used in-depth interviews to investigate the medical knowledge and clinical practices surrounding ADRD diagnoses among 42 healthcare workers employed at mid-tier health facilities in southwestern Uganda. Qualitative content analysis was used to identify distinct categories and themes.

Results

Our findings show that healthcare workers without specific mental health training assessed and diagnosed dementia based on history and physical examination alone. On the other hand, healthcare workers with some specialized training in mental health were more likely to use neuropsychological tests, blood tests, urine tests, and brain imaging in the diagnosis of dementia. Collateral history from caregivers was noted to be very important in proper assessment and diagnosis of dementia among all categories of healthcare workers. The majority of healthcare workers regarded memory loss as part of the normal aging process and reported that it does not need any specific treatment. Other healthcare workers could recognize signs and symptoms of dementia, but focused on managing other medical problems at the expense of assessing cognitive decline and mental health. Diagnostic practices did not differ based on age, years of experience, or gender of the healthcare workers.

Conclusion

These results indicate that specialized training in mental health among healthcare workers is crucial for the assessment and diagnosis of ADRD in rural southwestern Uganda.
Creating performance intelligence for primary health care strengthening in Europe
Authors: Barbazza Erica , Kringos Dionne , Kruse Ioana , Klazinga Niek S. , Tello Juan E.
Published: December 2019

Background

Primary health care and its strengthening through performance measurement is essential for sustainably working towards universal health coverage. Existing performance frameworks and indicators to measure primary health care capture system functions like governance, financing and resourcing but to a lesser extent the function of services delivery and its heterogeneous nature. Moreover, most frameworks have weak links with routine information systems and national health priorities, especially in the context of high- and middle-income countries. This paper presents the development of a tool that responds to this context with the aim to create primary health care performance intelligence for the 53 countries of the WHO European Region.

Methods

The work builds-off of an existing systematic review on primary care and draws on priorities of current European health policies and available (inter)national information systems. Its development included: (i) reviewing and classifying features of primary care; (ii) constructing a set of tracer conditions; and (iii) mapping existing indicators in the framework resulting from (i). The analysis was validated through a series of reviews: in-person meetings with country-nominated focal points and primary care experts; at-distance expert reviews; and, preliminary testing with country informants.

Results

The resulting framework applies aperformancecontinuum in the classical approach of structures-processes-outcomes spanning 6 domains – primary care structures, model of primary care, care contact, primary care outputs, health system outcomes, and health outcomes – that are further classified by 26 subdomains and 63 features of primary care. Acarecontinuum was developed using a set of 12 tracer conditions. A total of 139 indicators were mapped to the classification, each with an identified data source to safeguard measurability. Individual indicator passports and a glossary of terms were developed to support the standardization of the findings.

Conclusion

The resulting framework and suite of indicators, coined the Primary Health Care Impact, Performance and Capacity Tool (PHC-IMPACT), has the potential to be applied in Europe, closing the gap on existing data collection, analysis and use of performance intelligence for decision-making towards primary health care strengthening.
Molecular epidemiology and viremia of porcine astrovirus in pigs from Guangxi province of China
Authors: Qin Yifeng , Fang Qingli , Li Xunjie , Li Fakai , Liu Huan , Wei Zuzhang , Ouyang Kang , Chen Ying , Huang Weijian
Published: December 2019

Background

Porcine astroviruses (PAstVs) are common in pigs worldwide. There are five distinct lineages with each lineage representing a different ancestral origin. Recently, multiple reports have demonstrated the evidence of extra-intestinal infection of PAstVs, but little is known about viremia.

Results

In this study, a total of 532 fecal samples and 120 serum samples from healthy pigs were collected and tested from 2013 to 2015 in Guangxi province, China; of these 300/532 (56.4%) and 7/120 (5.8%) of fecal samples tested positive for PAstVs, respectively. Our study revealed that there was wide genetic diversity and high prevalence of the virus in the pig population. All five of the known PAstVs genotypes (1–5) prevailed in the pig population of Guangxi province and were distributed in all age groups of pigs, from suckling piglets to sows, with PAstV2 (47.7%), PAstV1 (26.2%) and PAstV5 (21.5%) seen predominantly. Phylogenetic analysis of partial ORF1b and partial capsid sequences from fecal and serum samples revealed that they were divided into the five lineages. Among these genotypes, based on partial ORF2 genes sequencing 23 strains were grouped as PAstV1, including 6 serum-derived strains, and were regarded as the causative agents of viremia in pigs.

Conclusions

Due to the information regarding the types of PAstV in blood is limit. This is the first report for the presence of PAstV1 in blood and PAstV3 in the feces of nursery pigs of China. This study provides a reference for understanding the prevalence and genetic evolution of PAstVs in pigs in Guangxi province, China. It also provides a new perspective for understanding of the extra-intestinal infection of PAstVs in pigs.
Analysis of gene expression profiles and protein-protein interaction networks in multiple tissues of systemic sclerosis
Authors: Karimizadeh Elham , Sharifi-Zarchi Ali , Nikaein Hassan , Salehi Seyedehsaba , Salamatian Bahar , Elmi Naser , Gharibdoost Farhad , Mahmoudi Mahdi
Published: December 2019

Background

Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The mechanisms underlying tissue pathology in SSc have not been entirely understood. This study intended to investigate the common and tissue-specific pathways involved in different tissues of SSc patients.

Methods

An integrative gene expression analysis of ten independent microarray datasets of three tissues was conducted to identify differentially expressed genes (DEGs). DEGs were mapped to the search tool for retrieval of interacting genes (STRING) to acquire protein–protein interaction (PPI) networks. Then, functional clusters in PPI networks were determined. Enrichr, a gene list enrichment analysis tool, was utilized for the functional enrichment of clusters.

Results

A total of 12, 2, and 4 functional clusters from 619, 52, and 119 DEGs were determined in the lung, peripheral blood mononuclear cell (PBMC), and skin tissues, respectively. Analysis revealed that the tumor necrosis factor (TNF) signaling pathway was enriched significantly in the three investigated tissues as a common pathway. In addition, clusters associated with inflammation and immunity were common in the three investigated tissues. However, clusters related to the fibrosis process were common in lung and skin tissues.

Conclusions

Analysis indicated that there were common pathological clusters that contributed to the pathogenesis of SSc in different tissues. Moreover, it seems that the common pathways in distinct tissues stem from a diverse set of genes.
miR-149 inhibits cell proliferation and enhances chemosensitivity by targeting CDC42 and BCL2 in neuroblastoma
Authors: Mao Fengxia , Zhang Ju , Cheng Xinru , Xu Qianya
Published: December 2019

Background

Neuroblastoma (NB) is one of most common childhood tumors with high mortality among children worldwide. microRNAs (miRNAs) have been reported to play essential roles in the pathogenesis and therapeutics of NB. However, the role of miR-149 and its mechanism remain poorly understood.

Main methods

The expression levels of miR-149, cell division cycle 42 (CDC42) and B-cell lymphoma 2 (BCL2) were measured in NB tissues or cells by quantitative real-time polymerase chain reaction or western blot. Cell proliferation was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation assays. Cell apoptosis was detected by flow cytometry. Chemosensitivity of NB cells to doxorubicin (Dox) was analyzed by MTT assay. The interaction between miR-149 and CDC42 or BCL2 was explored by luciferase activity and RNA immunoprecipitation analyses.

Results

Our data indicated that low expression of miR-149 was displayed in NB tissues and cells and associated with poor survival rate. Overexpression of miR-149 inhibited cell proliferation and colony formation but promoted cell apoptosis and chemosensitivity to Dox in NB cells. Moreover, CDC42 and BCL2 were targeted by miR-149. Additionally, CDC42 and BCL2 mRNA levels were elevated in NB tissues and cells and restoration of CDC42 or BCL2 reversed the regulatory effect of miR-149 on NB progression.

Conclusion

Our data suggested that miR-149 suppressed cell proliferation and improved Dox chemosensitivity by regulating CDC42 and BCL2 in NB, providing a novel avenue for treatment of NB.
Cumulative solar ultraviolet radiation exposure and basal cell carcinoma of the skin in a nationwide US cohort using satellite and ground-based measures
Authors: Little Mark P. , Linet Martha S. , Kimlin Michael G. , Lee Terrence , Tatalovich Zaria , Sigurdson Alice J. , Cahoon Elizabeth K.
Published: December 2019

Background

Basal cell carcinoma of the skin (BCC) is the most common cancer in populations of European ancestry. Although consistently linked with basal cell carcinoma of the skin in case-control studies, few prospective cohort studies have evaluated the shape of the exposure-response of basal cell carcinoma associated with cumulative radiant solar ultraviolet exposure (UVR).

Methods

We followed 63,912 white cancer-free US radiologic technologists from entry (1983–1998) to exit (2003–2005) with known ultraviolet irradiance at up to 5 residential locations. Using generalized-additive and relative risk models we analyzed the exposure-response of basal cell carcinomas associated with ambient cumulative ultraviolet radiant exposure using ground-based National Solar Radiation database Average Daily Total Global data and satellite-based National Aeronautics and Space Administration Total Ozone Mapping Spectrometer data.

Results

There were 2151 technologists with an incident primary basal cell carcinoma. Risk of basal cell carcinoma rose with increasing cumulative ultraviolet radiation exposure using both measures, such that 1 MJ cm− 2 increased basal cell carcinoma risk by 8.48 (95% CI 5.22, 11.09, p < 0.001) and by 10.15 (95% CI 6.67, 13.10, p < 0.001) per 10,000 persons per year using the Average Daily Total Global and Total Ozone Mapping Spectrometer ultraviolet data, respectively; relative risk was likewise elevated. There was some evidence of upward curvature in the cumulative ultraviolet exposure response using both exposure measures with a greater increase in risk of basal cell carcinoma at higher levels of ultraviolet radiation exposure, but less evidence for curvature in relative risk. There are indications of substantial variation of relative risk with time after exposure and age at exposure, so that risk is highest for the period 10–14 years after ultraviolet radiation exposure and for those exposed under the age of 25.

Conclusions

We observed increases in risk of basal cell carcinoma and a similar exposure-response for ground-based and satellite ultraviolet radiation measures. Our observations suggest that interventions should concentrate on persons with higher levels of ultraviolet radiation exposure.
Identification of diagnostic biomarkers in patients with gestational diabetes mellitus based on transcriptome gene expression and methylation correlation analysis
Authors: Li Enchun , Luo Tengfei , Wang Yingjun
Published: December 2019

Background

Gestational diabetes mellitus (GDM) has a high prevalence in the period of pregnancy. However, the lack of gold standards in current screening and diagnostic methods posed the biggest limitation. Regulation of gene expression caused by DNA methylation plays an important role in metabolic diseases. In this study, we aimed to screen GDM diagnostic markers, and establish a diagnostic model for predicting GDM.

Methods

First, we acquired data of DNA methylation and gene expression in GDM samples (N = 41) and normal samples (N = 41) from the Gene Expression Omnibus (GEO) database. After pre-processing the data, linear models were used to identify differentially expressed genes (DEGs). Then we performed pathway enrichment analysis to extract relationships among genes from pathways, construct pathway networks, and further analyzed the relationship between gene expression and methylation of promoter regions. We screened for genes which are significantly negatively correlated with methylation and established mRNA-mRNA-CpGs network. The network topology was further analyzed to screen hub genes which were recognized as robust GDM biomarkers. Finally, the samples were randomly divided into training set (N = 28) and internal verification set (N = 27), and the support vector machine (SVM) ten-fold cross-validation method was used to establish a diagnostic classifier, which verified on internal and external data sets.

Results

In this study, we identified 465 significant DEGs. Functional enrichment analysis revealed that these genes were associated with Type I diabetes mellitus and immunization. And we constructed an interactional network including 1091 genes by using the regulatory relationships of all 30 enriched pathways. 184 epigenetics regulated genes were screened by analyzing the relationship between gene expression and promoter regions’ methylation in the network. Moreover, the accuracy rate in the training data set was increased up to 96.3, and 82.1% in the internal validation set, and 97.3% in external validation data sets after establishing diagnostic classifiers which were performed by analyzing the gene expression profiles of obtained 10 hub genes from this network, combined with SVM.

Conclusions

This study provided new features for the diagnosis of GDM and may contribute to the diagnosis and personalized treatment of GDM.
Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in at-risk patient groups: pregnancy, elderly and obese patients
Authors: Brenner Benjamin , Arya Roopen , Beyer-Westendorf Jan , Douketis James , Hull Russell , Elalamy Ismail , Imberti Davide , Zhai Zhenguo
Published: December 2019

Background

Venous thromboembolism (VTE) accounts for an estimated 900,000 cases per year in the US alone and constitutes a considerable burden on healthcare systems across the globe.

Objective

To understand why the burden is so high, qualitative and quantitative research was carried out to gain insights from experts, guidelines and published studies on the unmet clinical needs and therapeutic strategies in VTE prevention and treatment in three populations identified as being at increased risk of VTE and in whom VTE prevention and treatment were regarded as suboptimal: pregnant women, the elderly and obese patients.

Methodology

A gap analysis methodology was created to highlight unmet needs in VTE management and to discover the patient populations considered most at risk. A questionnaire was devised to guide qualitative interviews with 44 thrombosis and haemostasis experts, and a review of the literature on VTE in the specific patient groups from 2015 to 2017 was completed. This was followed by a Think Tank meeting where the results from the research were discussed.

Results

This review highlights the insights gained and examines in detail the unmet needs with regard to VTE risk-assessment tools, biomarkers, patient stratification methods, and anticoagulant and dosing regimens in pregnant women, the elderly and obese patients.

Conclusions

Specifically, in pregnant women at high risk of VTE, low-molecular-weight heparin (LMWH) is the therapy of choice, but it remains unclear how to use anticoagulants when VTE risk is intermediate. In elderly patients, evaluation of the benefit of VTE prophylaxis against the bleeding risk is particularly important, and a head-to-head comparison of efficacy and safety of LMWH versus direct oral anticoagulants is needed. Finally, in obese patients, lack of guidance on anticoagulant dose adjustment to body weight has emerged as a major obstacle in effective prophylaxis and treatment of VTE.
Fostering implementation of knowledge into health practice: study protocol for the validation and redevelopment of the Knowledge Uptake and Utilization Tool
Authors: Shankar Sneha , Skinner Kelly , Morton Ninomiya Melody E. , Bhawra Jasmin
Published: December 2019

Background

Measurement of what knowledge is taken-up and how that information is used to inform practice and policies can provide an understanding about the effectiveness of knowledge uptake and utilization processes. In 2007, the Knowledge Uptake and Utilization Tool (KUUT) was developed to evaluate the implementation of knowledge into practice. The KUUT has been used by numerous large health organizations despite limited validity evidence and a narrow understanding about how the tool is used in practice and interpreted by users. As such, the overall purpose of this protocol is to redevelop the KUUT and gather validity evidence to examine and support its use in various health-related organizations. This protocol paper outlines a validation and redevelopment procedure for the KUUT using the unitary view of validity.

Methods

The protocol outlined in this article proceeds through four phases, starting with redeveloping the tool, then evaluating validity evidence based on: test content, response processes and internal structure. The initial phase gathers information to redevelop the tool, and evaluates item content and response format. The second phase evaluates response process validity evidence by examining how a variety of users interact with the tool. In the third phase, the tool will be pilot tested with knowledge users and, in the final phase, psychometric properties of the tool will be examined and a final scoring structure will be determined. A knowledge translation plan described herein outlines where the final tool will be housed and how the information about the tool will be disseminated.

Discussion

This protocol outlines a procedure to gather different sources of validity evidence for the KUUT. By addressing limitations in the original KUUT, such as complexities with scoring, a redeveloped KUUT supporting validity evidence will enhance the ability of health-related organizations to effectively use this tool for its intended purpose.
Chronic idiopathic musculoskeletal pain in youth: a qualitative study
Authors: Lefèvre Hervé , Loisel Alexandra , Meunier Brigitte Bader , Deslandre Chantal , Lemoine Noémie , Moro Marie Rose , Quartier Pierre , Lachal Jonathan
Published: December 2019

Background

Chronic musculoskeletal pain (MSP) is frequent in adolescents and has major medical and social consequences. In many cases, when no cause has been clearly established, this pain may be considered to be chronic idiopathic MSP. Our study seeks to identify general criteria for this type of pain through the experience of professionals from tertiary care centers with expertise in pediatric and adolescent chronic MSP.

Methods

Cross-sectional multicenter qualitative study. Semi-structured interviews of 25 professionals at a rheumatology reference center and in its network for pain management, including diverse specialists and professions. Interpretative Phenomenological Analysis is used to explore the data.

Results

This approach led us to identify 10 themes organized around three superordinate themes covering different stages of the diagnostic process: 1) the medical pain history up to the consultation at the reference center; 2) the professional’s subjective feelings about the clinical presentation; 3) from the clinical examination to diagnosis and treatment of chronic idiopathic MSP. The main elements guiding this diagnosis do not come from the physical examination but from the medical history and the professionals’ subjective feelings, that is, their clinical judgment. The professionals’ impression of uneasiness and frustration, induced by patients and their parents, is of major importance.

Conclusion

The principal elements guiding the diagnosis of chronic idiopathic MSP do not come primarily from the physical examination but rather from the pain history and the health professional’s subjective feelings. Our results suggest that the concept of Juvenile Fibromyalgia (JFM) does not appear to cover all situations of chronic idiopathic MSP in adolescence. A constellation of non-organic criteria enables diagnosis of the latter; these criteria should be validated to avoid medical nomadism and multiple investigations and to shorten the interval until patients receive optimal pain management.

Clinical trial registration

clinicaltrials.gov, NCT03171792, https://clinicaltrials.gov/ct2/show/NCT03171792?term=LACHAL&cntry=FR&city=paris&rank=1
Interleukin-1β drives NEDD8 nuclear-to-cytoplasmic translocation, fostering parkin activation via NEDD8 binding to the P-ubiquitin activating site
Authors: Balasubramaniam Meenakshisundaram , Parcon Paul A. , Bose Chhanda , Liu Ling , Jones Richard A. , Farlow Martin R. , Mrak Robert E. , Barger Steven W. , Griffin W. Sue T.
Published: December 2019

Background

Neuroinflammation, typified by elevated levels of interleukin-1 (IL-1) α and β, and deficits in proteostasis, characterized by accumulation of polyubiquitinated proteins and other aggregates, are associated with neurodegenerative disease independently and through interactions of the two phenomena. We investigated the influence of IL-1β on ubiquitination via its impact on activation of the E3 ligase parkin by either phosphorylated ubiquitin (P-Ub) or NEDD8.

Methods

Immunohistochemistry and Proximity Ligation Assay were used to assess colocalization of parkin with P-tau or NEDD8 in hippocampus from Alzheimer patients (AD) and controls. IL-1β effects on PINK1, P-Ub, parkin, P-parkin, and GSK3β—as well as phosphorylation of parkin by GSK3β—were assessed in cell cultures by western immunoblot, using two inhibitors and siRNA knockdown to suppress GSK3β. Computer modeling characterized the binding and the effects of P-Ub and NEDD8 on parkin. IL-1α, IL-1β, and parkin gene expression was assessed by RT-PCR in brains of 2- and 17-month-old PD-APP mice and wild-type littermates.

Results

IL-1α, IL-1β, and parkin mRNA levels were higher in PD-APP mice compared with wild-type littermates, and IL-1α-laden glia surrounded parkin- and P-tau-laden neurons in human AD. Such neurons showed a nuclear-to-cytoplasmic translocation of NEDD8 that was mimicked in IL-1β-treated primary neuronal cultures. These cultures also showed higher parkin levels and GSK3β-induced parkin phosphorylation; PINK1 levels were suppressed. In silico simulation predicted that binding of either P-Ub or NEDD8 at a singular position on parkin opens the UBL domain, exposing Ser65 for parkin activation.

Conclusions

The promotion of parkin- and NEDD8-mediated ubiquitination by IL-1β is consistent with an acute neuroprotective role. However, accumulations of P-tau and P-Ub and other elements of proteostasis, such as translocated NEDD8, in AD and in response to IL-1β suggest either over-stimulation or a proteostatic failure that may result from chronic IL-1β elevation, easily envisioned considering its early induction in Down’s syndrome and mild cognitive impairment. The findings further link autophagy and neuroinflammation, two important aspects of AD pathogenesis, which have previously been only loosely related.
Perceptions of isolation during facility births in Haiti - a qualitative study
Authors: Dev Alka , Kivland Chelsey , Faustin Mikerlyne , Turnier Olivia , Bell Tatiana , Leger Marie Denise
Published: December 2019

Background

Haiti’s maternal mortality, stillbirth, and neonatal mortality rates are the highest in Latin America and the Caribbean. Despite inherent risks, the majority of women still deliver at home without supervision from a skilled birth attendant. The purpose of this study was to elucidate factors driving this decision.

Methods

We conducted six focus group discussions with women living in urban (N = 14) or rural (N = 17) areas and asked them questions pertaining to their reasons for delivering at a facility or at home, perceptions of staff at the health facility, experiences with or knowledge of facility or home deliveries, and prior pregnancy experiences (if relevant). We also included currently pregnant women to learn about their plans for delivery, if any.

Results

All of the women interviewed acknowledged similar perceived benefits of a facility birth, which were a reduced risk of complications during pregnancy and access to emergency care. However, many women also reported unfavorable birthing experiences at facilities. We identified four key thematic concerns that underpinned women’s negative assessments of a facility birth: being left alone, feeling ignored, being subject to physical immobility, and lack of compassionate touch/care. Taken together, these concerns articulated an overarching sense of what we term “isolation,” which encompasses feelings of being isolated in the hospital during delivery.

Conclusion

Although Haitian women recognized that a facility was a safer place for birthing than the home, an overarching stigma of patient neglect and isolation in facilities was a major determining factor in choosing to deliver at home. The Haitian maternal mortality rate is high and will not be lowered if women continue to feel that they will not receive comfort and compassionate touch/care at a facility compared to their experience of delivering with traditional birth attendants at home. Based on these results, we recommend that all secondary and tertiary facilities offering labor and delivery services develop patient support programs, where women are better supported from admission through the labor and delivery process, including but not limited to improvements in communication, privacy, companionship (if deemed safe), respectful care, attention to pain during vaginal exams, and choice of birth position.
Structural parameters for X-ray micro-computed tomography (μCT) and their relationship with the breakage rate of maize varieties
Authors: Hou Junfeng , Zhang Ying , Jin Xiuliang , Dong Pengfei , Guo Yanan , Wang Keru , Fan Yinghu , Li Shaokun
Published: December 2019

Background

High grain breakage rate is the main limiting factor encountered in the mechanical harvest of maize grain. X-ray micro-computed tomography (μCT) scanning technology could be used to obtain the three-dimensional structure of maize grain. Currently, the effect of maize grain structure on the grain breakage rate, determined using X-ray μCT scanning technology, has not been reported. Therefore, the objectives of this study are: (i) to obtain the shape, geometry, and structural parameters related to the breakage rate using X-ray μCT scanning technology; (ii) to explore relationships between these parameters and grain breakage rate.

Result

In this study, 28 parameters were determined using X-ray μCT scanning technology. The maize breakage rate was mainly influenced by the grain specific surface area, subcutaneous cavity volume, sphericity, and density. In particular, the breakage rate was directly affected by the subcutaneous cavity volume and density. The maize variety with high density and low subcutaneous cavity volume had a low breakage rate. The specific surface area (r = 0.758*), embryo specific surface area (r = 0.927**), subcutaneous cavity volume ratio (0.581*), and subcutaneous cavity volume (0.589*) of maize grain significantly and positively correlated with breakage rate. The cavity specific surface area (− 0.628*) and grain density (− 0.934**) of maize grain significantly and negatively correlated with grain breakage rates. Grain shape (length, width, thickness, and aspect ratio) positively correlated with grain breakage rate but the correlation did not reach statistical significance. The susceptibility of grain breakage increased when kernel weight decreased (− 0.371), but the effect was not significant.

Conclusions

The results indicate that X-ray μCT scanning technology could be effectively used to evaluate maize grain breakage rate. X-ray μCT scanning technology provided a more precise and comprehensive acquisition method to evaluate the shape, geometry, and structure of maize grain. Thus, data gained by X-ray μCT can be used as a guideline for breeding resistant breakage maize varieties. Grain density and subcutaneous cavity volume are two of the most important factors affecting grain breakage rate. Grain density, in particular, plays a vital role in grain breakage and this parameter can be used to predict the breakage rate of maize varieties.
Retrospective analysis of fractionated intensity-modulated radiotherapy (IMRT) in the interdisciplinary management of primary optic nerve sheath meningiomas
Authors: Eckert Franziska , Clasen Kerstin , Kelbsch Carina , Tonagel Felix , Bender Benjamin , Tabatabai Ghazaleh , Zips Daniel , Thorwarth Daniela , Frey Bettina , Becker Gerd , Wilhelm Helmut , Paulsen Frank
Published: December 2019

Background

As optic nerve sheath meningiomas (ONSM) are rare, there are no prospective studies. Our retrospective analysis focusses on a cohort of patients with uniform disease characteristics all treated with the same radiotherapy regimen. We describe treatment decision making, radiotherapy planning and detailed neuro-ophthalmological outcome of the patients.

Methods

26 patients with unilateral ONSM extending only to the orbit and the optic canal were evaluated for neuro-ophthalmological outcome. Radiation treatment was planned in a simultaneous integrated boost approach to gross tumor volume (GTV) + 2 mm / 5 mm to 54 Gy / 51 Gy in 1.8 Gy / 1.7 Gy fractions. Follow-up was done by specialized neuro-ophthalmologists. Visual acuity and visual field defects were evaluated after therapy as well as during follow-up.

Results

Interdisciplinary treatment decision for patients with ONSM follows a rather complex decision tree. Radiation treatment planning (equivalent uniform dose (EUD), maximum dose to the optic nerve) improved with experience over time. With this patient selection visual acuity as well as visual field improved significantly at first follow-up after treatment. For visual acuity this also applied to patients with severe defects before treatment. Long term evaluation showed 16 patients with improved visual function, 6 were stable, in 4 patients visual function declined. Interdisciplinary case discussion rated the visual decline as radiation-associated in two patients.

Conclusions

With stringent patient selection radiotherapy for unilateral primary ONSM to 51 Gy / 54 Gy is safe and leads to significantly improved visual function. Interdisciplinary treatment decision and experience of the radiation oncology team play a major role.