bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and radiographic predictors of acute compartment syndrome in the treatment of tibial shaft fractures: a retrospective cohort study
Authors: Wuarin Lydia , Gonzalez Amanda I. , Zingg Matthieu , Belinga Patrick , Hoffmeyer Pierre , Peter Robin , Lübbeke Anne , Gamulin Axel
Published: January 2020

Background

The purpose of this study was to evaluate the association between epidemiological, clinical and radiographic factors of patients with tibial shaft fractures and the occurrence of acute compartment syndrome.

Methods

270 consecutive adult patients sustaining 273 tibial shaft fractures between January 2005 and December 2009 were included in this retrospective cohort study. The outcome measure was acute compartment syndrome. Patient-related (age, sex), fracture-related (high- vs. low-energy injury, isolated trauma vs. polytrauma, closed vs. open fracture) and radiological parameters (AO/OTA classification, presence or absence of a noncontiguous tibial plateau or pilon fracture, distance from the centre of the tibial fracture to the talar dome, distance between tibial and fibular fracture if associated, and angulation, translation and over-riding of main tibial fragments) were evaluated regarding their potential association with acute compartment syndrome. Univariate analysis was performed and each covariate was adjusted for age and sex. Finally, a multivariable logistic regression model was built, and odds ratios and 95% confidence intervals were obtained. Statistical significance was defined asp < 0.05.

Results

Acute compartment syndrome developed in 31 (11.4%) cases. In the multivariable regression model, four covariates remained statistically significantly associated with acute compartment syndrome: polytrauma, closed fracture, associated tibial plateau or pilon fracture and distance from the centre of the tibial fracture to the talar dome ≥15 cm.

Conclusions

One radiological parameter related to the occurrence of acute compartment syndrome has been highlighted in this study, namely a longer distance from the centre of the tibial fracture to the talar dome, meaning a more proximal fracture. This observation may be useful when clinical findings are difficult to assess (doubtful clinical signs, obtunded, sedated or intubated patients). However, larger studies are mandatory to confirm and refine the prediction of acute compartment syndrome occurrence. Radiographic signs of significant displacement were not found to be correlated to acute compartment syndrome development. Finally, the higher rate of acute compartment syndrome occurring in tibial shaft fractures associated to other musculoskeletal, thoraco-abdominal or cranio-cerebral injuries must raise the level of suspicion of any surgeon managing multiply injured patients.
Factors predicting one-year post-surgical mortality amongst older Asian patients undergoing moderate to major non-cardiac surgery – a retrospective cohort study
Authors: Liew Lydia Q. , Teo Wei Wei , Seet Edwin , Lean Lyn Li , Paramasivan Ambika , Tan Joanna , Lim Irene , Wang Jiexun , Ti Lian Kah
Published: January 2020

Background

While short-term perioperative outcomes have been well studied in Western surgical populations, the aim of this study is to look at the one-year perioperative mortality and its associated factors in an Asian surgical population after non-cardiac surgery.

Methods

A retrospective cohort study of 2163 patients aged above 45 undergoing non-cardiac surgery in a university-affiliated tertiary hospital from January to July 2015 was performed. Relevant demographic, clinical and surgical data were analysed to elicit their relationship to mortality at one year after surgery. A univariate analysis was first performed to identify significant variables with p-values ≤ 0.2, which were then analysed using Firth multiple logistic regression to calculate the adjusted odds ratio.

Results

The one-year mortality in our surgical population was 5.9%. The significant factors that increased one-year mortality include smoking (adjusted OR 2.17 (1.02–4.45), p = 0.044), anaemia (adjusted OR 1.32 (1.16–1.47), p < 0.001, for every 1 g/dL drop in haemoglobin level), lower BMI (adjusted OR 0.93 (0.87–0.98), p = 0.005, for every 1 point increase in BMI), Malay and Indian ethnicity (adjusted OR 2.68 (1.53–4.65), p = 0.001), peripheral vascular disease (adjusted OR 4.21 (1.62–10.38), p = 0.004), advanced age (adjusted OR 1.04 (1.01–1.06), p = 0.004, for every one year increase in age), emergency surgery (adjusted OR 2.26 (1.29–3.15), p = 0.005) and malignancy (adjusted OR 3.20 (1.85–5.52), p < 0.001).

Conclusions

Our study shows that modifiable risk factors such as malnutrition, anaemia and smoking which affect short term mortality extend beyond the immediate perioperative period into longer term outcomes. Identification and optimization of this subset of patients are therefore vital. Further similar large studies should be done to develop a risk scoring system for post-operative long-term outcomes. This would aid clinicians in risk stratification, counselling and surgical planning, which will help in patients’ decision making and care planning.
Characteristics of aggressive incidents in emergency primary health care described by the Staff Observation Aggression Scale – Revised Emergency (SOAS-RE)
Authors: Johnsen Grethe E. , Morken Tone , Baste Valborg , Rypdal Knut , Palmstierna Tom , Johansen Ingrid Hjulstad
Published: January 2020

Background

Workplace violence in emergency primary health care is prevalent, but longitudinal studies using validated assessment scales to describe the characteristics of workplace violence in these settings are lacking. The aim of the present study was to determine the characteristics of aggressive incidents in emergency primary health care clinics in Norway.

Methods

Incidents of workplace violence were reported with the Staff Observation Aggression Scale – Revised Emergency (SOAS-RE). The study was conducted in ten emergency primary health care clinics over a period of one year.

Results

A total of 320 aggressive incidents were registered. The mean overall SOAS-RE score for reported aggressive incidents was 9.7 on a scale from 0 to 22, and 60% of the incidents were considered severe. Incidents of verbal aggression accounted for 31.6% of all reported incidents, threats accounted for 24.7%, and physical aggression accounted for 43.7%. Verbal aggression was most often provoked by long waiting time. Physical aggression was most often provoked when the patient had to go through an involuntary assessment of health condition. Almost one third of the aggressors were females, and nurses were the most frequent targets of all aggression types. No differences in psychological stress were found between types of aggression.

Conclusions

This study shows that workplace violence in emergency primary health care clinics is a severe problem. Patterns in provocation and consequences of aggressive incidents can be used to improve our understanding of and prevention and follow-up procedures of such incidents.
N-acetyl-L-cysteine reduces Leishmania amazonensis-induced inflammation in BALB/c mice
Authors: Crupi Rosalia , Gugliandolo Enrico , Siracusa Rosalba , Impellizzeri Daniela , Cordaro Marika , Di Paola Rosanna , Britti Domenico , Cuzzocrea Salvatore
Published: January 2020

Background

Leishmaniasis is a emergent disease characterized by different clinical manifestations in both humans and dogs. Predominant clinical features of cutaneous leishmaniasis are ulcerative painless skin lesions. Several data reported that pain is associated with human and dog leishmaniasis, out with areas of painless ulcerative lesions per se. Actually, current medications used for leishmaniasis management are characterized by several side effects and, in addition, some cases of the disease are refractory to the treatment. On this background it is mandatory the identification of new and safe candidates for designing less toxic and low-cost remedies. Therefore, the search for new leishmanicidal compounds is indispensable.

Methods

In the present paper we investigated the effect of orally N-acetyl-L-cysteine (NAC) supplementation at dose of 200 mg/Kg for 10 weeks, in subcutaneousLeishmania(L).amazonensisinfected BALB/c mice. And evaluating the effect of NAC on inflammatory response such as TNF-α, IL-6, IL-1β levels, and on thermal and mechanical hyperalgesia.

Results

In the present paper we showed how NAC supplementation affected parameters of oxidative stress (GSH, MDA, SOD), inflammation such as cytokines levels (IL-1β, IL-6, TNFα) and mast cell activation and consequently on induced pain, during leishmaniosis in BALB\c mice.

Conclusions

The findings of our study provided the scientific data demonstrating thatL. amazonensisinfection induces inflammation and pain in BALB/c mice that are reversed by administration of NAC.
Mortality associated with wildfire smoke exposure in Washington state, 2006–2017: a case-crossover study
Authors: Doubleday Annie , Schulte Jill , Sheppard Lianne , Kadlec Matt , Dhammapala Ranil , Fox Julie , Busch Isaksen Tania
Published: January 2020

Background

Wildfire events are increasing in prevalence in the western United States. Research has found mixed results on the degree to which exposure to wildfire smoke is associated with an increased risk of mortality.

Methods

We tested for an association between exposure to wildfire smoke and non-traumatic mortality in Washington State, USA. We characterized wildfire smoke days as binary for grid cells based on daily average PM2.5 concentrations, from June 1 through September 30, 2006–2017. Wildfire smoke days were defined as all days with assigned monitor concentration above a PM2.5 value of 20.4 μg/m3, with an additional set of criteria applied to days between 9 and 20.4 μg/m3. We employed a case-crossover study design using conditional logistic regression and time-stratified referent sampling, controlling for humidex.

Results

The odds of all-ages non-traumatic mortality with same-day exposure was 1.0% (95% CI: − 1.0 - 4.0%) greater on wildfire smoke days compared to non-wildfire smoke days, and the previous day’s exposure was associated with a 2.0% (95% CI: 0.0–5.0%) increase. When stratified by cause of mortality, odds of same-day respiratory mortality increased by 9.0% (95% CI: 0.0–18.0%), while the odds of same-day COPD mortality increased by 14.0% (95% CI: 2.0–26.0%). In subgroup analyses, we observed a 35.0% (95% CI: 9.0–67.0%) increase in the odds of same-day respiratory mortality for adults ages 45–64.

Conclusions

This study suggests increased odds of mortality in the first few days following wildfire smoke exposure. It is the first to examine this relationship in Washington State and will help inform local and state risk communication efforts and decision-making during future wildfire smoke events.
Preclinical development of a novel CD47 nanobody with less toxicity and enhanced anti-cancer therapeutic potential
Authors: Ma Linlin , Zhu Min , Gai Junwei , Li Guanghui , Chang Qing , Qiao Peng , Cao Longlong , Chen Wanqing , Zhang Siyuan , Wan Yakun
Published: January 2020

Background

CD47, the integrin-related protein, plays an important role in immune resistance and escape of tumor cells. Antibodies blocking the CD47/SIRPα signal pathway can effectively stimulate macrophage-mediated phagocytosis of tumor cells, which becomes a promising approach for tumor immunotherapy. Nanobodies (Nbs) derived from camelid animals are emerging as a new force in antibody therapy.

Results

HuNb1-IgG4, an innovative anti-CD47 nanobody, was developed with high affinity and specificity. It effectively enhanced macrophage-mediated phagocytosis of tumor cells in vitro and showed potent anti-ovarian and anti-lymphoma activity in vivo. Importantly, HuNb1-IgG4 did not induce the agglutination of human red blood cells (RBCs) in vitro and exhibited high safety for hematopoietic system in cynomolgus monkey. In addition, HuNb1-IgG4 could be produced on a large scale in CHO-S cells with high activity and good stability. Also, we established anti-CD47/CD20 bispecific antibody (BsAb) consisted of HuNb1 and Rituximab, showing more preference binding to tumor cells and more potent anti-lymphoma activity compared to HuNb1-IgG4.

Conclusions

Both of HuNb1-IgG4 and anti-CD47/CD20 BsAb are potent antagonists of CD47/SIRPα pathway and promising candidates for clinical trials.
Early-stage cervical cancer diagnosis based on an ultra-sensitive electrochemical DNA nanobiosensor for HPV-18 detection in real samples
Authors: Mahmoodi Pegah , Rezayi Majid , Rasouli Elisa , Avan Amir , Gholami Mehrdad , Ghayour Mobarhan Majid , Karimi Ehsan , Alias Yatima
Published: January 2020

Background

In several years ago, infection with human papillomaviruses (HPVs), have been prevalent in the worlds especially HPV type 18, can lead to cervical cancer. Therefore, rapid, accurate, and early diagnosis of HPV for successful treatment is essential. The present study describes the development of a selective and sensitive electrochemical biosensor base on DNA, for early detection of HPV-18. For this purpose, a nanocomposite of reduced graphene oxide (rGO) and multiwalled carbon nanotubes (MWCNTs) were electrodeposited on a screen-printed carbon electrode (SPCE). Then, Au nanoparticles (AuNPs) were dropped on a modified SPCE. Subsequently, single strand DNA (ssDNA) probe was immobilized on the modified electrode. The link attached between AuNPs and probe ssDNA provided by l-cysteine via functionalizing AuNPs (Cys-AuNPs). The differential pulse voltammetry (DPV) assay was also used to electrochemical measurement. The measurement was based on the oxidation signals of anthraquninone-2-sulfonic acid monohydrate sodium salt (AQMS) before and after hybridization between the probe and target DNA.

Results

The calibration curve showed a linear range between 0.01 fM to 0.01 nM with a limit of detection 0.05 fM. The results showed that the optimum concentration for DNA probe was 5 µM. The good performance of the proposed biosensor was achieved through hybridization of DNA probe-modified SPCE with extracted DNA from clinical samples.

Conclusions

According to the investigated results, this biosensor can be introduced as a proprietary, accurate, sensitive, and rapid diagnostic method of HPV 18 in the polymerase chain reaction (PCR) of real samples.
Using life course charts to assess and compare trajectories of amphetamine type stimulant consumption in different user groups: a cross-sectional study
Authors: Martens Marcus-Sebastian , Zurhold Heike , Rosenkranz Moritz , O’Donnell Amy , Addison Michelle , Spencer Liam , McGovern William , Gabrhelík Roman , Petruželka Benjamin , Rowicka Magdalena , Liebregts Nienke , Degkwitz Peter , Kaner Eileen , Verthein Uwe
Published: January 2020

Background

Amphetamine-type stimulants (ATS) are the second most commonly used illicit drugs in Europe and globally. However, there is limited understanding of what shapes patterns of ATS use over the life course. The ATTUNE project “Understanding Pathways to Stimulant Use: a mixed methods examination of the individual, social and cultural factors shaping illicit stimulant use across Europe” aims to fill this gap. Here we report initial findings from the life course chart exercise conducted as part of qualitative interviews with ATS users and nonusers.

Methods

Two hundred seventy-nine in-depth qualitative interviews were conducted with five ATS user groups (current and former dependent users;current and former frequent users;non-frequent users) and one group of exposed non-ATS users in five European countries (Germany, UK, Poland, Netherlands and Czech Republic). As part of the interviews, we used life course charts to capture key life events and substance use histories. Life events were categorised as either positive, neutral or negative, and associated data were analysed systematically to identify differences between user groups. We applied statistical analysis of variance (ANOVA) and analysis of covariance (ANCOVA) to test for group differences.

Results

Out of 3547 life events documented, 1523 life events were categorised as neutral, 1005 life events as positive and 1019 life events as negative. Current and formerly dependent ATS users showed more negative life events for the entire life course after age adjustment. Although some group differences could be attributed to the individuals’ life course prior to first ATS use, most negative life events were associated with periods of ATS usage. A detailed analysis of the specific life domains reveals that dominantly, the social environment was affected by negative life events.

Conclusions

For non-dependent, frequent and non-frequent ATS users, negative life events from the period of ATS use do not become obvious in our analysed data. Besides preventing a pathway into ATS dependency, the aim of an intervention should be to reduce the harm by for example drug testing which offers also the opportunity for interventions to prevent developing a substance use dependency.

For the group of dependent ATS users, our study suggests holistic, tailored interventions and specialist treatment services are needed, as a single, simple intervention is unlikely to cover all the life domains affected.
Albumin-fibrinogen ratio and fibrinogen-prealbumin ratio as promising prognostic markers for cancers: an updated meta-analysis
Authors: Sun Da-wei , An Lin , Lv Guo-yue
Published: January 2020

Objective

Provide an updated and comprehensive evaluation of the prognostic value of the albumin-fibrinogen ratio (AFR) and the fibrinogen-prealbumin ratio (FPR) for patients with cancer.

Materials and methods

Four databases (PubMed, Web of Science, Cochrane Library, and WanFang) were searched. The primary endpoints were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Pooled data were synthesized using StataMP 14 and expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

This update examined 19 studies (7282 cases) that assessed the correlation of AFR with cancer prognosis. Pooled univariate and multivariate analyses indicated significant correlations of low AFR with poor OS (HR 2.18, 95%CI 1.87–2.55 and HR 1.75, 95%CI 1.54–2.00, respectively), poor DFS (HR 1.89, 95%CI 1.54–2.32 and HR 1.51, 95%CI 1.29–1.76, respectively), and poor PFS (HR 1.68, 95%CI 1.42–1.99 and HR 1.48, 95%CI 1.16–1.88, respectively). Pooled univariate and multivariate analyses of 6 studies (2232 cases) indicated high FPR significantly correlated with poor OS (HR 2.37, 95%CI 2.03–2.77 and HR 1.97, 95%CI 1.41–2.77, respectively). One study reported that high FPR correlated with poor DFS (univariate analysis: HR 2.20, 95%CI 1.35–3.57; multivariate analysis: HR 1.77, 95%CI 1.04–2.99) and one study reported a correlation of high FPR with poor PFS in univariate analysis alone (HR 1.79, 95%CI 1.11–2.88).

Conclusion

A low AFR and a high FPR correlated with increased risk of cancer mortality and recurrence. AFR and FPR may be promising prognostic markers for cancers.
Integrating evidence from research into decision-making for controlling endemic tropical diseases in South East Nigeria: perceptions of producers and users of evidence on barriers and solutions
Authors: Ezenwaka Uchenna , Mbachu Chinyere , Etiaba Enyi , Uzochukwu Benjamin , Onwujekwe Obinna
Published: January 2020

Background

Endemic tropical diseases (ETDs) constitute a significant health burden in resource-poor countries. Weak integration of research evidence into policy and practice poses a major challenge to the control of ETDs. This study was undertaken to explore barriers to the use of research evidence in decision-making for controlling ETDs. It also highlights potential strategies for addressing these barriers, including the gaps in research generation and utilisation in the context of endemic disease control.

Methods

Information on barriers and solutions to integrating research evidence into decision-making for controlling ETDs in Anambra State, Nigeria, was collected from 68 participants (producers and users of evidence) during structured discussions in a workshop. Participants were purposively selected and allocated to groups based on their current involvement in endemic disease control and expertise. Discussions were facilitated with a topic guide and detailed notes were taken by an appointed recorder. Outputs from the discussions were synthesised and analysed manually.

Results

Cross-cutting barriers include a weak research linkage between producers and users of evidence and weak capacity to undertake health policy and systems research (HPSR). Producers of evidence were purported to conceptualise and frame their research questions based on their academic interests and funders’ focus without recourse to the decision-makers. Conversely, poor demand for research evidence was reported among users of evidence. Another user barrier identified was moribund research units of the Department of Planning Research and Statistics within the State Ministry of Health. Potential solutions for addressing these barriers include creation of knowledge networks and partnerships between producers and users of evidence, institutionalisation of sustainable capacity-building of both parties in HPSR and revival of State research units.

Conclusions

Evidence-informed decision-making for controlling ETDs is limited by constraints in the interactions of some factors between the users (supply side) and producers (demand side) of evidence. These constraints could be solved through stronger research collaborations, institutionalisation of HPSR, and frameworks for getting research into policy and practice.
Methods to promote equity in health resource allocation in low- and middle-income countries: an overview
Authors: Love-Koh James , Griffin Susan , Kataika Edward , Revill Paul , Sibandze Sibusiso , Walker Simon
Published: January 2020

Unfair differences in healthcare access, utilisation, quality or health outcomes exist between and within countries around the world. Improving health equity is a stated objective for many governments and international organizations. We provide an overview of the major tools that have been developed to measure, evaluate and promote health equity, along with the data required to operationalise them.

Methods are organised into four key policy questions facing decision-makers: (i) what is the current level of inequity in health; (ii) does government health expenditure benefit the worst-off; (iii) can government health expenditure more effectively promote equity; and (iv) which interventions provide the best value for money in reducing inequity.

Benefit incidence analysis can be used to estimate the distribution of current public health sector expenditure, with geographical resource allocation formulae and health system reform being the main government policy levers for improving equity. Techniques from the economic evaluation literature, such as extended and distributional cost-effectiveness analysis can be used to identify ‘best buy’ interventions from a health equity perspective. A range of inequality metrics, from gap measures and slope indices to concentration indices and regression analysis, can be applied to these approaches to evaluate changes in equity.

Methods from the economics literature can provide policymakers with a toolkit for addressing multiple aspects of health equity, from outcomes to financial protection, and can be adapted to accommodate data commonly available in low- and middle-income settings.
Gli promotes tumor progression through regulating epithelial-mesenchymal transition in non–small-cell lung cancer
Authors: Jiang Long , Huang Jia , Hu Yingjie , Lu Peiji , Luo Qingquan , Wang Lei
Published: January 2020

Introduction

Lung cancer is the leading causes of cancer-related deaths globally. The most frequent histologic type of lung cancer is non–small-cell lung cancer (NSCLC). NSCLC often undergo epithelial-mesenchymal transition (EMT). The components that control this process are thus promising therapeutic targets.

Materials and methods

Gli/EMT protein expression levels were examined by western blot in paired NSCLC patient tissues and NSCLC cell lines. Functional analyses were performed to investigate SHH/Gli signaling and EMT in NSCLC cell lines. MTS cell viability, luciferase reporter, and western blot assays were performed to analyze pathway activity, while wound healing and transwell assays were executed to measure cell migration and invasion.

Results

Higher Gli1 expressions were detected in tumor samples than in paired normal tissues. Differential expression of EMT biomarkers and activation of p-AKT were observed in tumor tissues. N-Shh stimulation of cells significantly increased reporter activity in NSCLC cell lines, while Gli-i treatment of transfected cells showed less relative reporter activity. When subjected to both Gli-i and N-Shh treatment, NSCLC cell lines continued to demonstrate decreased Gli transcriptional activity. Gli inhibition is associated with decreased expression level of p-AKT, N-cadherin and Vimentin. Knockdown of both Gli1 and Gli2 showed decreased EMT, migrative and invasive ability. Cells stimulated by N-Shh demonstrated greater mobility. In addition, AKT-i treated cells also demonstrated inhibited EMT activity.

Conclusions

This study provides evidence for aberrant upregulation of the Gli signaling pathway and a strong association between expression of Gli versus AKT and EMT markers in NSCLC.
C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts
Authors: Shu Chi , Zha Haoran , Long Haixia , Wang Xinxin , Yang Fei , Gao Jianbao , Hu Chunyan , Zhou Li , Guo Bo , Zhu Bo
Published: January 2020

Background

Mounting evidence suggests that complement components promote tumor progression via modulating immune suppression, angiogenesis, or tumor cell proliferation. However, the role of C3a-C3aR signaling in regulating lung metastasis of breast cancer remains unknown.

Methods

We performed various ex-vivo and in-vivo assays. Genetic and pharmacological C3aR blockade models were applied to investigate the role of C3a-C3aR in metastasis of breast cancer.

Results

C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Mechanically, C3a-C3aR signaling augments pro-metastatic cytokine secretion and extracellular matrix components expression of CAFs via the activation of PI3K-AKT signaling. Genetic or pharmacological blockade of C3aR signaling effectively inhibited lung metastasis of breast cancer in mouse models.

Conclusions

C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.
Identification and transfer of spatial transcriptomics signatures for cancer diagnosis
Authors: Yoosuf Niyaz , Navarro José Fernández , Salmén Fredrik , Ståhl Patrik L. , Daub Carsten O.
Published: January 2020

Background

Distinguishing ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) regions in clinical biopsies constitutes a diagnostic challenge. Spatial transcriptomics (ST) is an in situ capturing method, which allows quantification and visualization of transcriptomes in individual tissue sections. In the past, studies have shown that breast cancer samples can be used to study their transcriptomes with spatial resolution in individual tissue sections. Previously, supervised machine learning methods were used in clinical studies to predict the clinical outcomes for cancer types.

Methods

We used four publicly available ST breast cancer datasets from breast tissue sections annotated by pathologists as non-malignant, DCIS, or IDC. We trained and tested a machine learning method (support vector machine) based on the expert annotation as well as based on automatic selection of cell types by their transcriptome profiles.

Results

We identified expression signatures for expert annotated regions (non-malignant, DCIS, and IDC) and build machine learning models. Classification results for 798 expression signature transcripts showed high coincidence with the expert pathologist annotation for DCIS (100%) and IDC (96%). Extending our analysis to include all 25,179 expressed transcripts resulted in an accuracy of 99% for DCIS and 98% for IDC. Further, classification based on an automatically identified expression signature covering all ST spots of tissue sections resulted in prediction accuracy of 95% for DCIS and 91% for IDC.

Conclusions

This concept study suggest that the ST signatures learned from expert selected breast cancer tissue sections can be used to identify breast cancer regions in whole tissue sections including regions not trained on. Furthermore, the identified expression signatures can classify cancer regions in tissue sections not used for training with high accuracy. Expert-generated but even automatically generated cancer signatures from ST data might be able to classify breast cancer regions and provide clinical decision support for pathologists in the future.
Nutrient-wide association study of 92 foods and nutrients and breast cancer risk
Authors: Heath Alicia K. , Muller David C. , van den Brandt Piet A. , Papadimitriou Nikos , Critselis Elena , Gunter Marc , Vineis Paolo , Weiderpass Elisabete , Fagherazzi Guy , Boeing Heiner , Ferrari Pietro , Olsen Anja , Tjønneland Anne , Arveux Patrick , Boutron-Ruault Marie-Christine , Mancini Francesca Romana , Kühn Tilman , Turzanski-Fortner Renée , Schulze Matthias B. , Karakatsani Anna , Thriskos Paschalis , Trichopoulou Antonia , Masala Giovanna , Contiero Paolo , Ricceri Fulvio , Panico Salvatore , Bueno-de-Mesquita Bas , Bakker Marije F. , van Gils Carla H. , Olsen Karina Standahl , Skeie Guri , Lasheras Cristina , Agudo Antonio , Rodríguez-Barranco Miguel , Sánchez Maria-José , Amiano Pilar , Chirlaque María-Dolores , Barricarte Aurelio , Drake Isabel , Ericson Ulrika , Johansson Ingegerd , Winkvist Anna , Key Tim , Freisling Heinz , His Mathilde , Huybrechts Inge , Christakoudi Sofia , Ellingjord-Dale Merete , Riboli Elio , Tsilidis Konstantinos K. , Tzoulaki Ioanna
Published: January 2020

Background

Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study.

Methods

Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS).

Results

Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03–1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03–1.06 and 1.04, 95% CI 1.02–1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94–0.98; 0.96, 95% CI 0.94–0.99; and 0.96, 95% CI 0.95–0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS.

Conclusions

Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
Optimal cultivation of Chlamydia requires testing of serum on individual species
Authors: Desai Malhar , Zhang Huirong , Fan Huizhou
Published: January 2020

Objective

This report is a side product of experiments aimed at identifying serum for culturing obligate intracellular bacteriaChlamydia trachomatisandC. muridarumin mouse fibroblast L929 cells.

Results

Of five commercial serum samples tested, two showed optimal efficiencies at supporting growth of the human pathogenChlamydia trachomatisas control fetal bovine serum, whereas two showed modest ~ 40% inhibitions in progeny production, and the remaining one showed a 20% inhibition. Three of the six sera poorly supported growth of the murine pathogenChlamydia muridarum, resulting in 73–90% reduction in progeny formation. Most significantly, the one with the strongest (90%)C. muridaruminhibition activity showed optimalC. trachomatis-supporting efficiency. These findings indicate that in laboratories that study multipleChlamydiaspecies, serum samples should be prescreened on a species basis. ConsideringChlamydialbiology and epidemiology, it may even be necessary to perform serum tests on a serovar- or strain-basis for studying some animal chlamydiae.
DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation
Authors: Islam Shajedul , Uehara Osamu , Matsuoka Hirofumi , Kuramitsu Yasuhiro , Adhikari Bhoj Raj , Hiraki Daichi , Toraya Seiko , Jayawardena Asiri , Saito Ichiro , Muthumala Malsantha , Nagayasu Hiroki , Abiko Yoshihiro , Chiba Itsuo
Published: January 2020

Background

DNA hypermethylation of tumor suppressor genes is observed in precancerous lesions and oral cancer of individuals with the habits of betel quid (BQ) chewing.SIRT1has been identified as playing a role in the maintenance of epithelial integrity, and its alteration is often related to carcinogenesis. However, the methylation and transcription status ofSIRT1in patients with BQ chewing-related oral cancer has not been investigated. We examined the methylation status ofSIRT1in paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) obtained from BQ chewing and non-chewing patients and in tissue samples from healthy control subjects. In addition, we examined whether the hypermethylation ofSIRT1followed by its transcriptional downregulation in the human gingival epithelial cells could be caused by arecoline, a major component of BQ. Furthermore, we investigated the methylation status ofSIRT1in smear samples of macroscopically healthy buccal mucosa from subjects with a habit of BQ chewing.

Results

SIRT1was significantly hypermethylated in tissue samples of OSCC from BQ chewers and non-chewers than in oral mucosa from healthy control subjects. Results also showed that the hypermethylation level ofSIRT1was significantly higher in OSCC of patients with BQ chewing habits than in those of non-chewing habits (p< 0.05). Our in vitro model showed that hypermethylation is followed by downregulation of the transcriptional level ofSIRT1(p< 0.05). The methylation levels ofSIRT1in the smear samples obtained from BQ chewing individuals were significantly higher than those in the samples obtained from individuals that did not chew BQ. The duration of BQ chewing habits was correlated positively to the frequency ofSIRT1hypermethylation (p< 0.05).

Conclusions

Our results suggest that DNA hypermethylation ofSIRT1is involved in the occurrence of oral cancer in BQ chewing patients and that hypermethylation in the oral mucosa of BQ chewers could be a predictive marker for the occurrence of malignant transformation. This is the first report that showed DNA hypermethylation in clinically healthy oral epithelium of BQ chewers. Our study shows evidence that DNA hypermethylation may be an early event of oral carcinogenesis prior to observable clinical changes.
Nrf2 activation through the PI3K/GSK-3 axis protects neuronal cells from Aβ-mediated oxidative and metabolic damage
Authors: Sotolongo Krystal , Ghiso Jorge , Rostagno Agueda
Published: January 2020

Background

Mounting evidence points to a crucial role of amyloid-β (Aβ) in the pathophysiology of Alzheimer’s disease (AD), a disorder in which brain glucose hypometabolism, downregulation of central elements of phosphorylation pathways, reduced ATP levels, and enhanced oxidative damage coexist, and sometimes precede, synaptic alterations and clinical manifestations. Since the brain has limited energy storage capacity, mitochondria play essential roles in maintaining the high levels of energy demand, but, as major consumers of oxygen, these organelles are also the most important generators of reactive oxygen species (ROS). Thus, it is not surprising that mitochondrial dysfunction is tightly linked to synaptic loss and AD pathophysiology. In spite of their relevance, the mechanistic links among ROS homeostasis, metabolic alterations, and cell bioenergetics, particularly in relation to Aβ, still remain elusive.

Methods

We have used classic biochemical and immunocytochemical approaches together with the evaluation of real-time changes in global energy metabolism in a Seahorse Metabolic Analyzer to provide insights into the detrimental role of oligAβ in SH-SY5Y and primary neurons testing their pharmacologic protection by small molecules.

Results

Our findings indicate that oligomeric Aβ induces a dramatic increase in ROS production and severely affects neuronal metabolism and bioenergetics. Assessment of global energy metabolism in real time demonstrated Aβ-mediated reduction in oxygen consumption affecting basal and maximal respiration and causing decreased ATP production. Pharmacologic targeting of Aβ-challenged neurons with a set of small molecules of known antioxidant and cytoprotective activity prevented the metabolic/bioenergetic changes induced by the peptide, fully restoring mitochondrial function while inducing an antioxidant response that counterbalanced the ROS production. Search for a mechanistic link among the protective small molecules tested identified the transcription factor Nrf2—compromised by age and downregulated in AD and transgenic models—as their main target and the PI3K/GSK-3 axis as the central pathway through which the compounds elicit their Aβ protective action.

Conclusions

Our study provides insights into the complex molecular mechanisms triggered by oligAβ which profoundly affect mitochondrial performance and argues for the inclusion of small molecules targeting the PI3K/GSK-3 axis and Nrf2-mediated pathways as part of the current or future combinatorial therapies.
Children with autism spectrum disorder produce more ambiguous and less socially meaningful facial expressions: an experimental study using random forest classifiers
Authors: Grossard Charline , Dapogny Arnaud , Cohen David , Bernheim Sacha , Juillet Estelle , Hamel Fanny , Hun Stéphanie , Bourgeois Jérémy , Pellerin Hugues , Serret Sylvie , Bailly Kevin , Chaby Laurence
Published: January 2020

Background

Computer vision combined with human annotation could offer a novel method for exploring facial expression (FE) dynamics in children with autism spectrum disorder (ASD).

Methods

We recruited 157 children with typical development (TD) and 36 children with ASD in Paris and Nice to perform two experimental tasks to produce FEs with emotional valence. FEs were explored by judging ratings and by random forest (RF) classifiers. To do so, we located a set of 49 facial landmarks in the task videos, we generated a set of geometric and appearance features and we used RF classifiers to explore how children with ASD differed from TD children when producing FEs.

Results

Using multivariate models including other factors known to predict FEs (age, gender, intellectual quotient, emotion subtype, cultural background), ratings from expert raters showed that children with ASD had more difficulty producing FEs than TD children. In addition, when we explored how RF classifiers performed, we found that classification tasks, except for those for sadness, were highly accurate and that RF classifiers needed more facial landmarks to achieve the best classification for children with ASD. Confusion matrices showed that when RF classifiers were tested in children with ASD, anger was often confounded with happiness.

Limitations

The sample size of the group of children with ASD was lower than that of the group of TD children. By using several control calculations, we tried to compensate for this limitation.

Conclusion

Children with ASD have more difficulty producing socially meaningful FEs. The computer vision methods we used to explore FE dynamics also highlight that the production of FEs in children with ASD carries more ambiguity.
Mapping the ischemic penumbra and predicting stroke progression in acute ischemic stroke: the overlooked role of susceptibility weighted imaging
Authors: Darwish Eman A. F. , Abdelhameed-El-Nouby Maha , Geneidy Eman
Published: January 2020

Objectives

Asymmetrically prominent veins (APVs) detected on susceptibility weighted imaging (SWI) in acute stroke patients are assumed to signify compromised cerebral perfusion. We aimed to explore the role of APVs in identifying the ischemic penumbra and predicting stroke progression in acute stroke patients

Methods

Twenty patients with a middle cerebral artery ischemic infarction presenting within 24 h of symptoms onset underwent SWI following our standard MR stroke protocol imaging sequences which included diffusion-weighted imaging (DWI). Follow-up (FUP) FLAIR images were obtained at least 5 days after the initial MRI study. The Alberta Stroke Program Early CT Score (ASPECTS) was used to determine the initial infarct size, extent of APVs and final infarct size on initial DWI, SWI, and FUP images respectively. For each patient, SWI was compared with DWI images to determine match/mismatch of their respective ASPECTS values and calculate mismatch scores, whereas acute DWI findings were compared with follow-up images to identify infarct growth (IG) and calculate infarction growth scores (IGS).

Results

IG occurred in 6/10 patients with a positive DWI-SWI mismatch and in none of the patients without a positive DWI-SWI mismatch. A positive DWI/SWI mismatch was significantly associated with IG (χ2 = 8.57, p = 0.0138, Cramer’s V = 0.65). A significant inverse correlation was found between SWI ASPECTS and IGS (rs = − 0.702, p = 0.001). DWI-SWI mismatch scores were strongly correlated with IGS. (rs = 0.788, p = 0.000)

Conclusion

A positive DWI-SWI mismatch is an indicator of the ischemic penumbra and a predictor of infarct expansion if left untreated.
The long-term effects of cancer survivorship on household assets
Authors: Pak Tae-Young , Kim Hyungsoo , Kim Kyoung Tae
Published: January 2020

Background

Less is known about the impact of cancer on household assets and household financial portfolio during which cancer survivors face higher mortality risk. Economic theory predicts that cancer survivors would deplete their wealth in such a way that meets immediate financial needs for treatment and that hedges the risk of anticipated medical expenses associated with recurrence. Building upon this prediction, we examine long-term changes in household assets in response to cancer diagnosis among middle-aged and elderly Americans (age ≥ 50).

Results

Using the 2000–2014 waves of the Health and Retirement Study, we estimated the household fixed effects regression that regresses household assets on time elapsed since cancer diagnosis (≤ 2 years, > 2 but ≤4 years, > 4 but ≤6 years, and > 6 but ≤8 years). Regression estimates were adjusted for demographic characteristics, general health condition, employment outcomes, and household economic attributes. Household assets were measured by total net worth as well as the amount of savings held in each asset category. The loss of household assets attributable to cancer was estimated to be $125,832 in 2015 dollars per household with a cancer patient. This change came from statistically significant reductions in investment assets, miscellaneous savings, real estate equity, and business equity, and increases in unsecured debt. We also found 17.2–28.0% increases in cash and cash-equivalent assets from + 2 years since diagnosis through the rest of the study periods. The accumulation of cash was observed for both the well-insured group (multiple coverages) and those with limited insurance (single coverage).

Conclusions

The results showed evidence of both asset depletion and precautionary accumulation of liquid assets among cancer survivors, which reduces risk exposure of household financial portfolio. Our findings highlighted that household asset is an important source of liquidity to finance cancer care and to absorb the expected expenditure risk associated with cancer recurrence. We also showed that health insurance provides limited coverage of health risks associated with cancer.
Early events following bovine leukaemia virus infection in calves with different alleles of the major histocompatibility complex DRB3 gene
Authors: Forletti Agustina , Lützelschwab Claudia María , Cepeda Rosana , Esteban Eduardo N. , Gutiérrez Silvina Elena
Published: January 2020

Cattle maintaining a low proviral load (LPL) status after bovine leukaemia virus (BLV) infection have been recognized as BLV controllers and non-transmitters to uninfected cattle in experimental and natural conditions. LPL has been associated with host genetics, mainly with the BoLA class II DRB3 gene. The aim of this work was to study the kinetics of BLV and the host response in Holstein calves carrying different BoLA-DRB3 alleles. Twenty BLV-free calves were inoculated with infected lymphocytes. Two calves were maintained uninfected as controls. Proviral load, total leukocyte and lymphocyte counts, anti-BLVgp51 titres and BLVp24 expression levels were determined in blood samples at various times post-inoculation. The viral load peaked at 30 days post-inoculation (dpi) in all animals. The viral load decreased steadily from seroconversion (38 dpi) to the end of the study (178 dpi) in calves carrying a resistance-associated allele (*0902), while it was maintained at elevated levels in calves with *1501 or neutral alleles after seroconversion. Leukocyte and lymphocyte counts and BLVp24 expression did not significantly differ between genetic groups. Animals with < 20 proviral copies/30 ng of DNA at 178 dpi or < 200 proviral copies at 88 dpi were classified as LPL, while calves with levels above these limits were considered to have high proviral load (HPL) profiles. All six calves with the *1501 allele progressed to HPL, while LPL was attained by 6/7 (86%) and 2/6 (33%) of the calves with the *0902 and neutral alleles, respectively. One calf with both *0902 and *1501 developed LPL. This is the first report of experimental induction of the LPL profile in cattle.