bluuebunny/crossref_metadata_2025 huggingface dataset:
A targeted promotional DVD fails to improve Māori and Pacific participation rates in the New Zealand bowel screening pilot: results from a pseudo-randomised controlled trial
Authors: Bartholomew Karen , Zhou Lifeng , Crengle Sue , Buswell Elizabeth , Buckley Anne , Sandiford Peter
Published: September 2019

Background

New Zealand’s Bowel Screening Pilot (BSP) used a mailed invitation to return a faecal immunochemical test. As a pilot it offered opportunities to test interventions for reducing ethnic inequities in colorectal cancer screening prior to nationwide programme introduction. Small media interventions (e.g. educational material and DVDs) have been used at both community and participant level to improve uptake. We tested whether a DVD originally produced to raise community awareness among the Māori population would have a positive impact on participation and reduce the proportion of incorrectly performed tests (spoiled kits) if mailed out with the usual reminder letter.

Methods

The study was a parallel groups pseudo-randomised controlled trial. Over 12 months, all Māori and Pacific ethnicity non-responders four weeks after being mailed the test kit were allocated on alternate weeks to be sent, or not, the DVD intervention with the usual reminder letter. The objective was to determine changes in participation and spoiled kit rates in each ethnic group, determined three months from the date the reminder letter was sent. Participants and those recording the outcomes (receipt of a spoiled or non-spoiled test kit) were blinded to group assignment.

Results

2333 Māori and 2938 Pacific people participated (11 withdrew). Those who were sent the DVD (1029 Māori and 1359 Pacific) were less likely to participate in screening than those who were not (1304 Māori and 1579 Pacific). Screening participation was reduced by 12.3% (95% CI 9.1–15.5%) in Māori (13.6% versus 25.9%) and 8.3% (95% CI 5.8–10.8%) in Pacific (10.1% versus 18.4%). However, spoiled kit rates (first return) were significantly higher among those not sent the DVD (33.1% versus 12.4% in Māori and 42.1% versus 21.9% in Pacific).

Conclusion

The DVD sent with the reminder letter to BSP non-responders reduced screening participation to an extent that more than offset the lower rate of spoiled kits.

Trial registration

Australia and New Zealand Clinical Trials Registry ACTRN12612001259831. Registered 30 November 2013.
A systematic review of the effectiveness of digital interventions for illicit substance misuse harm reduction in third-level students
Authors: Dick Samantha , Whelan Eadaoin , Davoren Martin P. , Dockray Samantha , Heavin Ciara , Linehan Conor , Byrne Michael
Published: September 2019

Background

Illicit substance misuse is a growing public health problem, with misuse peaking among 18–25 year-olds, and attendance at third-level education identified as a risk factor. Illicit substance misuse has the potential to harm mental and physical health, social relationships, and impact on academic achievements and future career prospects. Digital interventions have been identified as a vehicle for reaching large student populations and circumventing the limited capacity of student health services for delivering face-to-face interventions. Digital interventions have been developed in the area of alcohol and tobacco harm reduction, reporting some effectiveness, but the evidence for the effectiveness of digital interventions targeting illicit substance misuse is lacking. This review aims to systematically identify and critically appraise studies examining the effectiveness of digital interventions for illicit substance misuse harm reduction in third-level students.

Methods

We systematically searched ten databases in April 2018 using keywords and database specific terms under the pillars of “mHealth,” “substance misuse,” and “student.” To be eligible for inclusion, papers had to present a measure of illicit substance misuse harm reduction. Included articles were critically appraised and included in the qualitative synthesis regardless of quality.

Results

A total of eight studies were included in the qualitative synthesis. Studies reported harm reduction in terms of substance misuse or initiation, as consequences or problems associated with substance misuse, or as correction of perceived social norms. Overall, five out of the eight studies reported at least one positive outcome for harm reduction. The critical appraisal indicated that the study quality was generally weak, predominantly due to a lack of blinding of study participants, and the use of self-reported substance misuse measures. However, results suggest that digital interventions may produce a modest reduction in harm from illicit substance misuse.

Conclusions

The results of this review are positive, and support the need for further high-quality research in this area, particularly given the success of digital interventions for alcohol and tobacco harm reduction. However, very few studies focused solely on illicit substances, and those that did targeted only marijuana. This suggests the need for further research on the effectiveness of this type of intervention for other illicit substances.

Trial registration

This review is registered on PROSPERO, ID number: CRD42018097203.
LncRNA PLAC 2 downregulated miR-21 in non-small cell lung cancer and predicted survival
Authors: Xia Huan , Xiu Ming , Gao Jinying , Jing Hongyu
Published: September 2019

Background

LncRNA PLAC2 has been characterized as a tumor suppressive lncRNA in glioma. We investigated the role of PLAC2 in non-small cell lung cancer (NSCLC).

Methods

A total of 187 NSCLC patients were admitted by The First Hospital of Jilin University from December 2010 to December 2014. All the patients were diagnosed by histopathological approaches. Transient cell transfections, RT-qPCR, invasion, and migration ability measurement, were applied for the experiments.

Results

PLAC2 was down-regulated, while miR-21 was up-regulated in NSCLC tissues compared to non-cancer tissues. Low PLAC2 levels in NSCLC tissues were associated with poor survival of NSCLC patients. PLAC2 and miR-21 were inversely correlated, and PLAC 2 over-expression in NSCLC cells resulted in the down-regulation of miR-21. However, miR-21 over-expression did not significantly affect PLAC2 expression. In addition, PLAC2 over-expression resulted in decreased migration and invasion rates of NSCLC cells. MiR-21 over-expression played the opposite role and attenuated the effects of PLAC2 over-expression.

Conclusions

In conclusion, lncRNA PLAC2 down-regulated miR-21 in NSCLC and inhibited cancer cell migration and invasion.
Circadian rhythm of COPD symptoms in clinically based phenotypes. Results from the STORICO Italian observational study
Authors:   on behalf of STORICO study group, Scichilone Nicola , Antonelli Incalzi Raffaele , Blasi Francesco , Schino Pietro , Cuttitta Giuseppina , Zullo Alessandro , Ori Alessandra , Canonica Giorgio Walter
Published: September 2019

Background

Chronic Obstructive Pulmonary Disease (COPD) encompasses various phenotypes that severely limit the applicability of precision respiratory medicine. The present investigation is aimed to assess the circadian rhythm of symptoms in pre-defined clinical COPD phenotypes and its association with health-related quality of life (HR-QoL), the quality of sleep and the level of depression/anxiety in each clinical phenotype.

Methods

The STORICO (NCT03105999) Italian observational prospective cohort study enrolled COPD subjects. A clinical diagnosis of either chronic bronchitis (CB), emphysema (EM) or mixed COPD-asthma (MCA) phenotype was made by clinicians at enrollment. Baseline early-morning, day-time and nocturnal symptoms (gathered via the Night-time, Morning and Day-time Symptoms of COPD questionnaire), HR-QoL (via the St. George’s Respiratory Questionnaire), anxiety and depression levels (via the Hospital Anxiety and Depression Scale), quality of sleep (via COPD and Asthma Sleep Impact Scale), physical activity (via the International Physical Activity Questionnaire) as well as lung function were recorded.

Results

606 COPD subjects (age 71.4 ± 8.2 years, male 75.1%) were studied. 57.9, 35.5 5.3 and 1.3% of the sample belonged to the CB, EM, MCA and EM + CB phenotypes respectively. The vast majority of subjects reported early-morning and day-time symptoms (79.5 and 79.2% in the CB and 75.8 and 77.7% in the EM groups); the proportion suffering from night-time symptoms was higher in the CB than in the EM group (53.6% vs. 39.5%, p = 0.0016). In both CB and EM, indiscriminately, the presence of symptoms during the 24-h day was associated with poorer HR-QoL, worse quality of sleep and higher levels of anxiety/depression.

Conclusions

The findings highlight the primary classificatory role of nocturnal symptoms in COPD.

Trial registration

Trial registration number: NCT03105999, date of registration: 10th April 2017.
Novel biodegradable magnesium alloy clips compared with titanium clips for hepatectomy in a rat model
Authors: Urade Takeshi , Yoshida Toshihiko , Ikeo Naoko , Naka Kosuke , Kido Masahiro , Toyama Hirochika , Ueno Kimihiko , Tanaka Motofumi , Mukai Toshiji , Fukumoto Takumi
Published: September 2019

Background

The use of surgical metal clips is crucial for ligating vessels in various operations. The currently available metal clips have several drawbacks; they are permanent and interfere with imaging techniques such as computed tomography (CT) or magnetic resonance (MR) imaging and carry the potential risk of endo-clip migration. We recently developed a novel magnesium (Mg) alloy for biodegradable clips that reduces artifacts on CT imaging. This study aimed to examine the tolerance, biodegradability, and biocompatibility of the Mg alloy clips compared with those of standard titanium (Ti) clips in hepatectomy.

Methods

Thirty Wistar rats were divided into two groups based on the clip used (groups A and B). The vascular pedicle, including hepatic artery, portal vein, bile duct, and hepatic vein of the left lateral lobe, was ligated with the Ti clip in group A or the Mg alloy clip in group B, and then the left lateral lobe was removed. The rats were sacrificed at 1, 4, 12, 24, and 36 weeks after surgery. Clinical and histological evaluations were performed. Absorption rate was calculated by measuring the clip volume.

Results

Although the Mg alloy clips showed biodegradability over time, there were no significant differences in the serum concentration of Mg between the two groups. The remaining volume ratio of Mg alloy clips was 95.5, 94.3, 80.0, 36.2, and 16.7% at 1, 4, 12, 24, and 36 weeks, respectively. No side effects occurred. Most of the microscopic changes were similar in both groups.

Conclusions

The new biodegradable Mg alloy clips are safe and feasible in vessel ligation for hepatectomy in a rat model and reduce artifacts in CT imaging compared with the standard Ti clips.
Efficacy analysis of two surgical treatments for thoracic and lumbar intraspinal tumours
Authors: Song Zhaojun , Zhang Zhi , Ye Yongjie , Zheng Jiazhuang , Wang Fandong
Published: September 2019

Background

Surgery remains the main curative option for the treatment of intraspinal tumour. The purpose of the present study was to analyze the clinical outcomes of laminoplasty with process-lamina complex replantation compared with laminectomy with pedicle screw fixation for intraspinal tumours.

Methods

In our retrospective analysis, 27 patients received tumour resection surgery by laminoplasty with reconstruction plate fixation and 32 patients received laminectomy with pedicle screw fixation. All patients were followed up for at least 1 year. Data, including surgical time, blood loss, volume of drainage, drainage time, hospital stay, complications, and neurological status were compared. In addition, imaging evaluation was also included.

Results

Patients in the laminoplasty group had lower blood loss (laminoplasty group: 281.5 ± 130.2 mL; laminectomy group: 450.0 ± 224.3 mL; p = 0.001), shorter surgical time (laminoplasty group: 141.7 ± 26.2 min, laminectomy group: 175.3 ± 50.4 min; p = 0.003), lower volume of drainage (laminoplasty group: 1578.9 ± 821.7 mL, laminectomy group: 2621.2 ± 1351.0 mL; p = 0.001), shorter drainage time (laminoplasty group: 6.6 ± 2.5 days, laminectomy group: 9.7 ± 1.8 days; p = 0.000), and a shorter hospital stay (laminoplasty group: 16.9 ± 4.9 days, laminectomy group: 21.0 ± 4.4 days; p = 0.002) compared with patients in the laminectomy group. There were significant differences of oswestry dysfunction index (ODI) between the two groups at 12 months postoperatively (p = 0.034). The incidence of secondary spinal stenosis in the laminoplasty group was significantly reduced (p = 0.029).

Conclusions

Laminoplasty in intraspinal tumour resection has a lower blood loss and volume of drainage, shorter surgical time and hospital stay as advantages over the standard laminectomy technique. Moreover, laminoplasty can effectively avoid iatrogenic spinal canal stenosis and thus enhancing functional recovery of spinal cord.
Quality of Life (QoL) among medical students in Saudi Arabia: a study using the WHOQOL-BREF instrument
Authors: Malibary Husam , Zagzoog Mohammad M. , Banjari Maysaa A. , Bamashmous Ryan O. , Omer Anoud R.
Published: September 2019

Background

Poor Quality of Life (QoL) among medical students is associated with an unhealthy lifestyle, psychological distress, and academic failure, which could affect their care for patients in the future. This study aimed to evaluate the reliability and validity of the Arabic WHOQOL-BREF tool among Saudi medical students and to assess the effect of gender, educational level, and academic performance on their QoL.

Methods

This was a cross-sectional study among medical students of King Abdulaziz University in February 2016, using the Arabic version of the WHOQOL-BREF instrument.

Results

Six-hundred-thirty medical students were included, where females constituted (51.1%). Cronbach’s α coefficient for the overall domains of WHOQOL-BREF was 0.86. Students’ self-reported QoL mean score was 3.99 ± 0.95, and their mean score for the overall satisfaction with health was 3.66 ± 1.06. The environmental domain had the highest mean score (67.81 ± 17.39). High achievers showed lower psychological health, while poor academic performance was associated with better psychological health and social relationship QoL scores (P < 0.013 andP < 0.014, respectively).

Conclusions

The WHOQOL-BREF is valid and reliable for assessing QoL among Saudi medical students. Although gender and academic year had no impact on the students’ QoL, better-performing students reported lower psychological health and social relationships scores.
Implementing the skilled birth attendance strategy in Uganda: a policy analysis
Authors: Munabi-Babigumira Susan , Nabudere Harriet , Asiimwe Delius , Fretheim Atle , Sandberg Kristin
Published: September 2019

Background

Uganda, a low resource country, implemented the skilled attendance at birth strategy, to meet a key target of the 5th Millenium Development Goal (MDG), 75% reduction in maternal mortality ratio. Maternal mortality rates remained high, despite the improvement in facility delivery rates. In this paper, we analyse the strategies implemented and bottlenecks experienced as Uganda’s skilled birth attendance policy was rolled out. These experiences provide important lessons for decision makers as they implement policies to further improve maternity care.

Methods

This is a case study of the implementation process, involving a document review and in-depth interviews among key informants selected from the Ministry of Health, Professional Organisations, Ugandan Parliament, the Health Service Commission, the private not-for-profit sector, non-government organisations, and District Health Officers. The Walt and Gilson health policy triangle guided data collection and analysis.

Results

The skilled birth attendance policy was an important priority on Uganda’s maternal health agenda and received strong political commitment, and support from development partners and national stakeholders. Considerable effort was devoted to implementation of this policy through strategies to increase the availability of skilled health workers for instance through expanded midwifery training, and creation of the comprehensive nurse midwife cadre. In addition, access to emergency obstetric care improved to some extent as the physical infrastructure expanded, and distribution of medicines and supplies improved. However, health worker recruitment was slow in part due to the restrictive staff norms that were remnants of previous policies. Despite considerable resources allocated to creating the comprehensive nurse midwife cadre, this resulted in nurses that lacked midwifery skills, while the training of specialised midwives reduced. The rate of expansion of the physical infrastructure outpaced the available human resources, equipment, blood infrastructure, and several health facilities were not fully functional.

Conclusion

Uganda’s skilled birth attendance policy aimed to increase access to obstetric care, but recruitment of human resources, and infrastructural capacity to provide good quality care remain a challenge. This study highlights the complex issues and unexpected consequences of policy implementation. Further evaluation of this policy is needed as decision-makers develop strategies to improve access to skilled care at birth.
Estimating the burden of dengue and the impact of release of wMel Wolbachia-infected mosquitoes in Indonesia: a modelling study
Authors: O’Reilly Kathleen M. , Hendrickx Emilie , Kharisma Dinar D. , Wilastonegoro Nandyan N. , Carrington Lauren B. , Elyazar Iqbal R. F. , Kucharski Adam J. , Lowe Rachel , Flasche Stefan , Pigott David M. , Reiner Robert C. , Edmunds W. John , Hay Simon I. , Yakob Laith , Shepard Donald S. , Brady Oliver J.
Published: September 2019

Background

Wolbachia-infected mosquitoes reduce dengue virus transmission, and city-wide releases in Yogyakarta city, Indonesia, are showing promising entomological results. Accurate estimates of the burden of dengue, its spatial distribution and the potential impact ofWolbachiaare critical in guiding funder and government decisions on its future wider use.

Methods

Here, we combine multiple modelling methods for burden estimation to predict national case burden disaggregated by severity and map the distribution of burden across the country using three separate data sources. An ensemble of transmission models then predicts the estimated reduction in dengue transmission following a nationwide roll-out of wMelWolbachia.

Results

We estimate that 7.8 million (95% uncertainty interval [UI] 1.8–17.7 million) symptomatic dengue cases occurred in Indonesia in 2015 and were associated with 332,865 (UI 94,175–754,203) lost disability-adjusted life years (DALYs). The majority of dengue’s burden was due to non-severe cases that did not seek treatment or were challenging to diagnose in outpatient settings leading to substantial underreporting. Estimated burden was highly concentrated in a small number of large cities with 90% of dengue cases occurring in 15.3% of land area. Implementing a nationwideWolbachiapopulation replacement programme was estimated to avert 86.2% (UI 36.2–99.9%) of cases over a long-term average.

Conclusions

These results suggest interventions targeted to the highest burden cities can have a disproportionate impact on dengue burden. Area-wide interventions, such asWolbachia, that are deployed based on the area covered could protect people more efficiently than individual-based interventions, such as vaccines, in such dense environments.
Engineering Pseudomonas putida for isoprenoid production by manipulating endogenous and shunt pathways supplying precursors
Authors: Hernandez-Arranz Sofía , Perez-Gil Jordi , Marshall-Sabey Dominic , Rodriguez-Concepcion Manuel
Published: September 2019

Background

The soil bacterium Pseudomonas putida is a promising platform for the production of industrially valuable natural compounds. In the case of isoprenoids, the availability of biosynthetic precursors is a major limiting factor. In P. putida and most other bacteria, these precursors are produced from pyruvate and glyceraldehyde 3-phosphate by the methylerythritol 4-phosphate (MEP) pathway, whereas other bacteria synthesize the same precursors from acetyl-CoA using the unrelated mevalonate (MVA) pathway.

Results

Here we explored different strategies to increase the supply of isoprenoid precursors in P. putida cells using lycopene as a read-out. Because we were not aiming at producing high isoprenoid titers but were primarily interested in finding ways to enhance the metabolic flux to isoprenoids, we engineered the well-characterized P. putida strain KT2440 to produce low but detectable levels of lycopene under conditions in which MEP pathway steps were not saturated. Then, we compared lycopene production in cells expressing the Myxococcus xanthus MVA pathway genes or endogenous MEP pathway genes (dxs, dxr, idi) under the control of IPTG-induced and stress-regulated promoters. We also tested a shunt pathway producing isoprenoid precursors from ribulose 5-phosphate using a mutant version of the Escherichia coli ribB gene.

Conclusions

The most successful combination led to a 50-fold increase in lycopene levels, indicating that P. putida can be successfully engineered to substantially increase the supply of metabolic substrates for the production of industrially valuable isoprenoids.
PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer
Authors: Jiang Cui , Cao SunRun , Li Na , Jiang Lei , Sun Tao
Published: September 2019

Background

Immunotherapies that targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have obtained prominent success in breast cancer (BC). However, not all the patients benefit from the antibody therapy. This study aimed to identify PD-1/PD-L1 correlated genes and pathways as well as investigate their potential as prognostic marker in BC.

Materials and methods

By analysing transcriptional data of BC from TCGA, we identified PD-1 and PD-L1 correlated genes by WGCNA analysis and explored the biological process as well as pathways they enriched. Co-expression analysis were performed for PD-1/PD-L1 with immune infiltration and checkpoints. The prognostic value of PD-1 and PD-L1 were also investigated.

Results

PD-1 and PD-L1 expression showed significant difference in different molecular subtypes and stages. PD-1 correlated genes enriched in T cell activation, lymphocyte activation, leukocyte migration while PD-L1 correlated genes demonstrated enrichment including T cell apoptotic process, tolerance induction and cytolysis. Immune infiltration analysis suggested that PD-1 and PD-L1 were related with Neutrophils (r = 0.65, r = 0.48) and Fibroblasts (r = 0.59, r = 0.47). For immune checkpoints analysis, PD-1 was associated with HLA-A (r = 0.804) and INPP5D (r = 0.782) while PD-L1 correlated with CTLA4 (r = 0.843) and CD27 (r = 0.823). PD-1 was associated favorable survival of BC (HR = 0.67, P = 0.012) while PD-L1 did not demonstrate significant association with BC prognosis (HR = 0.85, P = 0.313).

Conclusion

PD-1 and PD-L1 correlated genes participated in biological process including T cell activation, lymphocyte activation, leukocyte migration, T cell apoptotic process, tolerance induction and cytolysis. PD-1/PD-L1 expression also demonstrated relation with immune infiltration and immune checkpoints. High PD-1 expression predicted better survival of breast cancer patients.
Nonlytic exocytosis of Cryptococcus neoformans from neutrophils in the brain vasculature
Authors: Yang Xiaofan , Wang Huijuan , Hu Fan , Chen Xichen , Zhang Mingshun
Published: September 2019

Background

Cryptococcus neoformans (C. neoformans) is an encapsulated budding yeast that causes life-threatening meningoencephalitis in immunocompromised individuals, especially those with acquired immunodeficiency syndrome (AIDS). To cause meningoencephalitis, C. neoformans circulating in the bloodstream must first be arrested in the brain microvasculature. Neutrophils, the most abundant phagocytes in the bloodstream and the first leukocytes to be recruited to an infection site, can ingest C. neoformans. Little is known about how neutrophils interact with arrested fungal cells in the brain microvasculature.

Methods

A blood-brain barrier (BBB) in vitro model was established. The interactions between neutrophils adhering to brain endothelial cells and fungi were observed under a live cell imaging microscope. A flow cytometry assay was developed to explore the mechanisms. Immunofluorescence staining of brain tissues was utilized to validate the in vitro phenomena.

Results

Using real-time imaging, we observed that neutrophils adhered to a monolayer of mouse brain endothelial cells could expel ingested C. neoformans without lysis of the neutrophils or fungi in vitro, demonstrating nonlytic exocytosis of fungal cells from neutrophils. Furthermore, nonlytic exocytosis of C. neoformans from neutrophils was influenced by either the fungus (capsule and viability) or the neutrophil (phagosomal pH and actin polymerization). Moreover, nonlytic exocytosis of C. neoformans from neutrophils was recorded in brain tissue.

Conclusion

These results highlight a novel function by which neutrophils extrude C. neoformans in the brain vasculature.

Graphical abstract
CXCL1-LCN2 paracrine axis promotes progression of prostate cancer via the Src activation and epithelial-mesenchymal transition
Authors: Lu Yongning , Dong Baijun , Xu Fan , Xu Yunze , Pan Jiahua , Song Jiajia , Zhang Jin , Huang Yiran , Xue Wei
Published: September 2019

Background

Mechanisms driving the progression of castration-resistant prostate cancer are believed to relate substantially to the tumor microenvironment. However, the cross-talks between tumor epithelial cell, stromal cells, and immune cells are yet to be fully elucidated. The present study aims to determine the role of chemokine and neutrophil derived cytokine paracrine axis in mediating the interaction between tumor cells, stromal myofibroblasts, and neutrophils in the tumor microenvironment of prostate cancer.

Methods

To identify myofibroblasts and neutrophil derived specific proteins affecting progression of prostate cancer, bioinformatics analyses were firstly performed in independent human prostate cancer gene expression data sets from the GEO data bank. Expression of stromal myofibroblasts secretory chemokine CXCL1 and neutrophil derived cytokine LCN2 was evaluated in prostate tissues via immunohistochemistry assay. We further investigated the effect of CXCL1 and LCN2 on prostate cancer using in vivo and in vitro models, and explored the underlying signal transduction pathways.

Results

A CXCL1-LCN2 paracrine network was confirmed in prostate cancer tissue samples, which was correlated with the biochemical recurrence of prostate cancer. Of note, CXCL1-LCN2 axis activates Src signaling, triggers the epithelial-mesenchymal transition (EMT), consequently promotes the migration of prostate cancer cells, leading to enhanced tumor metastasis.

Conclusions

Our findings may provide enhanced insight into the interactions of carcinoma-stromal cells and immune cells linked to prostate cancer progression, wherein CXCL1-LCN2 axis is a key contributor to prostate cancer cells migration. These data indicate tumor microenvironment and Src signaling pathway may be potential therapeutic targets of prostate cancer treatment.
Biofluid quantification of TWEAK/Fn14 axis in combination with a selected biomarker panel improves assessment of prostate cancer aggressiveness
Authors: Ruiz-Plazas Xavier , Rodríguez-Gallego Esther , Alves Marta , Altuna-Coy Antonio , Lozano-Bartolomé Javier , Portero-Otin Manel , García-Fontgivell Joan Francesc , Martínez-González Salomé , Segarra José , Chacón Matilde R.
Published: September 2019

Background

Conventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness.

Methods

We collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression ofKLK2,KLK3,Fn14,CD163,CXCR2andCCR3was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness.

Results

Total serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels ofFn14,KLK2,CXCR2andCCR3in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782–1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613–0.830).

Conclusions

TWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.
The reliability and validity of the Patient Health Questionnaire-9 (PHQ-9) and PHQ-2 in patients with infertility
Authors: Maroufizadeh Saman , Omani-Samani Reza , Almasi-Hashiani Amir , Amini Payam , Sepidarkish Mahdi
Published: September 2019

Background

Depression in patients with infertility often goes undiagnosed and untreated. The Patient Health Questionnaire-9 (PHQ-9) and its ultra-brief version (i.e. PHQ-2) are widely used measures of depressive symptoms. These scales have not been validated in patients with infertility. The aim of the present study was to examine the reliability and validity of the PHQ-9 and PHQ-2 in patients with infertility.

Methods

In this cross-sectional study, a total of 539 patients with infertility from a referral infertility clinic in Tehran, Iran completed the PHQ-9, along with other relevant scales: the WHO-five Well-being Index (WHO-5), the Hospital Anxiety and Depression Scale (HADS), and the Generalized Anxiety Disorder-7 (GAD-7). Factor structure and internal consistency of PHQ-9 were examined via confirmatory factor analysis (CFA) and Cronbach’s alpha, respectively. Convergent validity was evaluated by relationship with WHO-5, HADS and GAD-7.

Results

The mean total PHQ-9 and PHQ-2 scores were 8.47 ± 6.17 and 2.42 ± 1.86, respectively, and using a cut-off value of 10 (for PHQ-9) and 3 (for PHQ-2), the prevalence of depressive symptoms was 38.6 and 43.6%, respectively. The Cronbach’s alphas for PHQ-9 and PHQ-2 were, respectively, 0.851 and 0.767, indicating good internal consistency. The CFA results confirmed the one-factor model of the PHQ-9 (χ2/df = 4.29; CFI = 0.98; RMSEA = 0.078 and SRMR = 0.044). Both PHQ-9 and PHQ-2 showed moderate to strong correlation with the measures of WHO-5, HADS-depression, HADS-anxiety, and the GAD-7, confirming convergent validity. In univariate analysis, female sex, long infertility duration, and unsuccessful treatment were significantly associated with depression symptoms.

Conclusion

Both PHQ-9 and PHQ-2 are brief and easy to use measures of depressive symptoms with good psychometric properties that appear suitable for routine use in patients with infertility.
The glocalization of antimicrobial stewardship
Authors: Rubin Olivier
Published: September 2019

This brief commentary argues that glocal governance introduces a fruitful new perspective to the global governance debate of AMR, and cautions against too strict a focus on establishing globally binding governance regimes for curbing AMR.
Endoscopic hemostasis followed by preventive transarterial embolization in high-risk patients with bleeding peptic ulcer: 5-year experience
Authors: Kaminskis Aleksejs , Ivanova Patricija , Kratovska Aina , Ponomarjova Sanita , Ptašņuka Margarita , Demičevs Jevgenijs , Demičeva Renate , Boka Viesturs , Pupelis Guntars
Published: September 2019

Background

Upper gastrointestinal bleeding (UGIB) due to peptic ulcer disease is one of the leading causes of death in patients with non-variceal bleeding, resulting in up to 10% mortality rate, and the patient group at high risk of rebleeding (Forrest IA, IB, and IIA) often requires additional therapy after endoscopic hemostasis. Preventive transarterial embolization (P-TAE) after endoscopic hemostasis was introduced in our institution in 2014. The aim of the study is an assessment of the intermediate results of P-TAE following primary endoscopic hemostasis in patients with serious comorbid conditions and high risk of rebleeding.

Methods

During the period from 2014 to 2018, a total of 399 patients referred to our institution with a bleeding peptic ulcer, classified as type Forrest IA, IB, or IIA with the Rockall score ≥ 5, after endoscopic hemostasis was prospectively included in two groups—P-TAE group and control group, where endoscopy alone (EA) was performed. The P-TAE patients underwent flow-reducing left gastric artery or gastroduodenal artery embolization according to the ulcer type. The rebleeding rate, complications, frequency of surgical interventions, transfused packed red blood cells (PRBC), amount of fresh frozen plasma (FFP), and mortality rate were analyzed.

Results

From 738 patients with a bleeding peptic ulcer, 399 were at high risk for rebleeding after endoscopic hemostasis. From this cohort, 58 patients underwent P-TAE, and 341 were allocated to the EA. A significantly lower rebleeding rate was observed in the P-TAE group, 3.4% vs. 16.2% in the EA group;p= 0.005. The need for surgical intervention reached 10.3% vs. 20.6% in the P-TAE and EA groups accordingly;p= 0.065. Patients that underwent P-TAE required less FFP, 1.3 unit vs. 2.6 units in EA;p= 0.0001. The mortality rate was similar in groups with a tendency to decrease in the P-TAE group, 5.7% vs. 8.5% in EA;p= 0.417.

Conclusion

P-TAE is a feasible and safe procedure, and it may reduce the rebleeding rate and the need for surgical intervention in patients with a bleeding peptic ulcer when the rebleeding risk remains high after primary endoscopic hemostasis.
Skeletonisation contributing to a reduction of sternal wound complications: a retrospective study in OPCAB patients
Authors: Van den Eynde Jef , Heeren Astrid , Szecel Delphine , Meuris Bart , Jacobs Steven , Verbrugghe Peter , Oosterlinck Wouter
Published: September 2019

Background

Sternal wound complications (SWC) are a rare but potentially life-threatening complication after coronary artery bypass grafting (CABG) surgery. Especially the use of bilateral IMA (BIMA) grafts as opposed to single IMA (SIMA) grafts is associated with an increased risk of SWC. Skeletonised harvesting has been proposed to reduce this risk. The purpose of this study was to retrospectively investigate the effect of skeletonisation on SWC after off-pump coronary artery bypass grafting (OPCAB) in a centre with a high volume of off-pump procedures and high frequencies of BIMA.

Methods

From January 2010 to November 2016, 1900 consecutive patients underwent OPCAB surgery at the University Hospitals of Leuven. The first group (n = 1487) received non-skeletonised IMA grafts, whereas the second group (n = 413) received skeletonised grafts. Optimal wound management was pursued in all patients. A new four-grade classification for SWC was developed. Incidence and grade of SWC as well as overall survival were assessed.

Results

Analysis of diabetic patients showed a lower incidence of SWC in the skeletonised (12/141, 8.5%) compared to the non-skeletonised group (82/414, 19.8%) [odds ratio 0.46, 95% confidence interval (0.23;0.88), p = 0.019] as well as a lower grade [0.45 (0.24;0.871), p = 0.018]. There was no significant effect on overall survival [0.67 (0.19;2.32), p = 0.529]. Subanalysis of this population revealed that the observed effects were most prominent in patients receiving BIMA grafts, with 6/56 (10.7%) SWC in the skeletonised and 62/252 (24.6%) in the non-skeletonised group [0.37 (0.15;0.90), p = 0.028 for incidence], as well as a lower grade [0.36 (0.15;0.88), p = 0.025]. These advantages were not significant in diabetic patients receiving SIMA grafts nor in the full study population.

Conclusions

This study, using a more sensitive classification of SWC, shows in a large group of patients that, in combination with optimized wound management, the skeletonisation technique is associated with a clear reduction in the incidence and grade of SWC in diabetic patients receiving BIMA grafts. This encourages the extension of BIMA use in OPCAB to this risk population.
Gingival metastasis of a mediastinal pulmonary sarcomatoid carcinoma: a case report
Authors: Qin Zhonghua , Huang Bin , Yu Guiping , Zheng Yongqiang , Zhao Ke
Published: September 2019

Background

Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy with both epithelial and sarcoma components, and high tumor metastasis potential.

Case presentation

A 63-year-old male patient had a tumor in the right posterior mediastinum, and was eventually diagnosed with PSC and gingival metastasis. The patient underwent thoracoscopic right upper pneumonectomy with lymph node dissections, and the subsequent gingival biopsy revealed a metastatic PSC. The immunohistochemistry revealed that both PSC site tissues were positive for vimentin, CKAE1/AE3 and Ki-67. The patient received radiotherapy and chemotherapy after surgery, and deceased two months later due to systemic tumor metastases.

Conclusion

PSC metastasis is variable, and leads to diagnostic dilemma or erroneous diagnosis. A differential diagnosis can help to distinguish it from gingival cancer.
A comparison of automatic cell identification methods for single-cell RNA sequencing data
Authors: Abdelaal Tamim , Michielsen Lieke , Cats Davy , Hoogduin Dylan , Mei Hailiang , Reinders Marcel J. T. , Mahfouz Ahmed
Published: September 2019

Background

Single-cell transcriptomics is rapidly advancing our understanding of the cellular composition of complex tissues and organisms. A major limitation in most analysis pipelines is the reliance on manual annotations to determine cell identities, which are time-consuming and irreproducible. The exponential growth in the number of cells and samples has prompted the adaptation and development of supervised classification methods for automatic cell identification.

Results

Here, we benchmarked 22 classification methods that automatically assign cell identities including single-cell-specific and general-purpose classifiers. The performance of the methods is evaluated using 27 publicly available single-cell RNA sequencing datasets of different sizes, technologies, species, and levels of complexity. We use 2 experimental setups to evaluate the performance of each method for within dataset predictions (intra-dataset) and across datasets (inter-dataset) based on accuracy, percentage of unclassified cells, and computation time. We further evaluate the methods’ sensitivity to the input features, number of cells per population, and their performance across different annotation levels and datasets. We find that most classifiers perform well on a variety of datasets with decreased accuracy for complex datasets with overlapping classes or deep annotations. The general-purpose support vector machine classifier has overall the best performance across the different experiments.

Conclusions

We present a comprehensive evaluation of automatic cell identification methods for single-cell RNA sequencing data. All the code used for the evaluation is available on GitHub (https://github.com/tabdelaal/scRNAseq_Benchmark). Additionally, we provide a Snakemake workflow to facilitate the benchmarking and to support the extension of new methods and new datasets.
scBFA: modeling detection patterns to mitigate technical noise in large-scale single-cell genomics data
Authors: Li Ruoxin , Quon Gerald
Published: September 2019

Technical variation in feature measurements, such as gene expression and locus accessibility, is a key challenge of large-scale single-cell genomic datasets. We show that this technical variation in both scRNA-seq and scATAC-seq datasets can be mitigated by analyzing feature detection patterns alone and ignoring feature quantification measurements. This result holds when datasets have low detection noise relative to quantification noise. We demonstrate state-of-the-art performance of detection pattern models using our new framework, scBFA, for both cell type identification and trajectory inference. Performance gains can also be realized in one line of R code in existing pipelines.
Strengthening Referral Networks for Management of Hypertension Across the Health System (STRENGTHS) in western Kenya: a study protocol of a cluster randomized trial
Authors: Mercer Tim , Njuguna Benson , Bloomfield Gerald S. , Dick Jonathan , Finkelstein Eric , Kamano Jemima , Mwangi Ann , Naanyu Violet , Pastakia Sonak D. , Valente Thomas W. , Vedanthan Rajesh , Akwanalo Constantine
Published: September 2019

Background

Hypertension is a major risk factor for cardiovascular disease (CVD), yet treatment and control rates for hypertension are very low in low- and middle-income countries (LMICs). Lack of effective referral networks between different levels of the health system is one factor that threatens the ability to achieve adequate blood pressure control and prevent CVD-related morbidity. Health information technology and peer support are two strategies that have improved care coordination and clinical outcomes for other disease entities in other settings; however, their effectiveness and cost-effectiveness in strengthening referral networks to improve blood pressure control and reduce CVD risk in low-resource settings are unknown.

Methods/design

We will use the PRECEDE-PROCEED framework to conduct transdisciplinary implementation research, focused on strengthening referral networks for hypertension in western Kenya. We will conduct a baseline needs and contextual assessment using a mixed-methods approach, in order to inform a participatory, community-based design process to fully develop a contextually and culturally appropriate intervention model that combines health information technology and peer support. Subsequently, we will conduct a two-arm cluster randomized trial comparing 1) usual care for referrals vs 2) referral networks strengthened with our intervention. The primary outcome will be one-year change in systolic blood pressure. The key secondary clinical outcome will be CVD risk reduction, and the key secondary implementation outcomes will include referral process metrics such as referral appropriateness and completion rates. We will conduct a mediation analysis to evaluate the influence of changes in referral network characteristics on intervention outcomes, a moderation analysis to evaluate the influence of baseline referral network characteristics on the effectiveness of the intervention, as well as a process evaluation using the Saunders framework. Finally, we will analyze the incremental cost-effectiveness of the intervention relative to usual care, in terms of costs per unit decrease in systolic blood pressure, per percentage change in CVD risk score, and per disability-adjusted life year saved.

Discussion

This study will provide evidence for the implementation of innovative strategies for strengthening referral networks to improve hypertension control in LMICs. If effective, it has the potential to be a scalable model for health systems strengthening in other low-resource settings worldwide.

Trial registration

Clinicaltrials.gov, NCT03543787. Registered on 29 June 2018.
Prevalence and associated factors of chronic kidney disease among adult hypertensive patients in Tigray teaching hospitals: a cross-sectional study
Authors: Bahrey Degena , Gebremedhn Gebreamlak , Mariye Teklewoini , Girmay Alem , Aberhe Woldu , Hika Assefa , Teklay Girmay , Tasew Hagos , Zeru Teklay , Gerensea Hadgu , Demoz Gebre Teklemariam
Published: September 2019

Objective

The aim of this study was to assess the prevalence of chronic kidney disease and to identify associated factors of chronic kidney disease among hypertensive patients. A cross-sectional study was conducted among selected 578 hypertensive patients. Data were collected using face to face interviewing questionnaires and from medical chart review. Binary logistic regression analyses were performed and analyzed using SPSS version 23.0.

Result

Of the total 578 hypertensive patients the prevalence of chronic kidney disease was found to be 128 (22.1%). Of these hypertensive patients, patients with uncontrolled blood pressure, overweight/obesity, dyslipidemia and diabetic mellitus, 43.3%, 33.7%, 27.3% and 28.2 respectively. After adjustment, the independent variables the significant associated factors of chronic kidney disease among hypertensive patients were age [AOR (95% CI 1.43 (1.07–1.81)], uncontrolled hypertension 4.434 [AOR (95% CI 9.45 (1.34, 14.73)], overweight/obese [AOR (95% CI 7.422 (2.72, 20.28)], dyslipidemia [AOR (95% CI) 13.749 (5.69, 33.215)], diabetic mellitus [AOR (95% CI) 2.137 (1.07, 4.26)]. In conclusion, the prevalence of chronic kidney disease was considerably high. The major associated factors of chronic kidney disease were age, uncontrolled hypertension, overweight/obese, diabetic mellitus and dyslipidemia.
Sketching for sequential change-point detection
Authors: Cao Yang , Thompson Andrew , Wang Meng , Xie Yao
Published: September 2019

We present sequential change-point detection procedures based on linear sketches of high-dimensional signal vectors using generalized likelihood ratio (GLR) statistics. The GLR statistics allow for an unknown post-change mean that represents an anomaly or novelty. We consider both fixed and time-varying projections, derive theoretical approximations to two fundamental performance metrics: the average run length (ARL) and the expected detection delay (EDD); these approximations are shown to be highly accurate by numerical simulations. We further characterize the relative performance measure of the sketching procedure compared to that without sketching and show that there can be little performance loss when the signal strength is sufficiently large, and enough number of sketches are used. Finally, we demonstrate the good performance of sketching procedures using simulation and real-data examples on solar flare detection and failure detection in power networks.