bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis
Authors: Yang Da-Wei , Wang Tong-Min , Zhang Jiang-Bo , Li Xi-Zhao , He Yong-Qiao , Xiao Ruowen , Xue Wen-Qiong , Zheng Xiao-Hui , Zhang Pei-Fen , Zhang Shao-Dan , Hu Ye-Zhu , Shen Guo-Ping , Chen Mingyuan , Sun Ying , Jia Wei-Hua
Published: June 2020

Background

Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor management. Radiogenomics studies have indicated that genetic variants are associated with adverse effects of radiotherapy.

Methods

A large-scale genome-wide scan was performed in 1467 nasopharyngeal carcinoma patients, including 753 treated with 2D-CRT from Genetic Architecture of the Radiotherapy Toxicity and Prognosis (GARTP) cohort and 714 treated with IMRT (192 from the GARTP and 522 newly recruited). Subgroup analysis by radiotherapy technique was further performed in the top associations. We also performed physical and regulatory mapping of the risk loci and gene set enrichment analysis of the candidate target genes.

Results

We identified 50 associated genomic loci and 64 genes via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping and gene-based analysis, and 36 of these loci were replicated in subgroup analysis. Interestingly, one of the top loci located in TNKS, a gene relevant to radiation toxicity, was associated with increased OM risk with OR = 3.72 of the lead SNP rs117157809 (95% CI 2.10–6.57; P = 6.33 × 10−6). Gene set analyses showed that the 64 candidate target genes were enriched in the biological processes of regulating telomere capping and maintenance and telomerase activity (Top P = 7.73 × 10−7).

Conclusions

These results enhance the biological understanding of radiotherapy toxicity. The association signals enriched in telomere function regulation implicate the potential underlying mechanism and warrant further functional investigation and potential individual radiotherapy applications.
Prevalence of co-existing autoimmune disease in juvenile idiopathic arthritis: a cross-sectional study
Authors: Simon Teresa A. , Harikrishnan Gowri Priya , Kawabata Hugh , Singhal Sanket , Brunner Hermine I. , Lovell Daniel J.
Published: June 2020

Background

Many autoimmune diseases share common pathogenic mechanisms, cytokine pathways and systemic inflammatory cascades; however, large studies quantifying the co-existence of autoimmune diseases in patients with juvenile idiopathic arthritis (JIA) have not been conducted.

Methods

We performed a cross-sectional study using two United States administrative healthcare claims databases (Truven Health MarketScan® Commercial Database and IMS PharMetrics database) to screen for the prevalence of multiple autoimmune diseases in patients with JIA and in a control group with attention deficit hyperactivity disorder (ADHD). Patients with a diagnosis code for JIA or ADHD between January 1, 2006 and September 30, 2017 were separated into two age cohorts (< 18 and ≥ 18 years) and matched (maximum 1:5) based on age, sex, number of medical encounters, and calendar year of diagnosis. The prevalence rates of 30 pre-specified autoimmune diseases during the 12-month periods before and after diagnosis were compared.

Results

Overall, 29,215 patients with JIA and 134,625 matched control patients with ADHD were evaluated. Among patients in the MarketScan database, 28/30 autoimmune diseases were more prevalent in patients with JIA aged < 18 years and 29/30 were more prevalent in patients aged ≥ 18 years when compared with a matched cohort of patients with ADHD. In the PharMetrics database, 29/30 and 30/30 autoimmune diseases were more prevalent in patients with JIA aged < 18 and ≥ 18 years, respectively, compared with a matched cohort of patients with ADHD. Among patients with JIA aged < 18 years, the greatest odds ratios (ORs) were seen for Sjögren’s syndrome/sicca syndrome and uveitis. Among patients aged ≥ 18 years in the MarketScan database, the greatest ORs were recorded for uveitis. Data from the PharMetrics database indicated that the greatest ORs were for uveitis and chronic glomerulonephritis.

Conclusions

Patients with JIA are more likely to have concurrent autoimmune diseases than matched patients with ADHD. Having an awareness of the co-existence of autoimmune diseases among patients with JIA may play an important role in patient management, treatment decisions, and outcomes.

Trial registration

Not applicable.
Testing a home-based model of care using misoprostol for prevention and treatment of postpartum hemorrhage: results from a randomized placebo-controlled trial conducted in Badakhshan province, Afghanistan
Authors: Abbas Dina F. , Mirzazada Shafiq , Durocher Jill , Pamiri Shahfaqir , Byrne Meagan E. , Winikoff Beverly
Published: June 2020

Background

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide. In Afghanistan, where most births take place at home without the assistance of a skilled birth attendant, there is a need for options to manage PPH in community-based settings. Misoprostol, a uterotonic that has been used as prophylaxis at the household level and has also been proven to be effective in treating PPH in hospital settings, is one possible option.

Methods

A double-blind, randomized placebo-controlled trial was conducted in six districts in Badakhshan Province, Afghanistan to test the effectiveness and safety of administering 800mcg sublingual misoprostol to women after a home birth for treatment of excessive blood loss. Consenting women were enrolled prior to delivery and given 600mcg misoprostol to self-administer orally as prophylaxis. Community health workers (CHW) were trained to observe for signs of PPH after delivery and if PPH was diagnosed, administer the study medication (misoprostol or placebo) and immediately refer the woman. A hemoglobin (Hb) decline of 2 g/dL or greater, measured pre- and post-delivery, served as the primary outcome; side effects, additional interventions, and transfer rates were also analyzed.

Results

Among the 1884 women who delivered at home, nearly all (98.7%) reported self-use of misoprostol for PPH prevention. A small fraction was diagnosed with PPH (4.4%, 82/1884) and was administered treatment. Hb outcomes, including the proportion of women with a Hb drop of 2 g/dL or greater, were similar between the study groups (misoprostol: 56.4% (22/39), placebo: 60.6% (20/33), p = 0.45). Significantly more women randomized to receive misoprostol experienced shivering (82.5% vs. placebo: 61.5%, p = 0.03). Other side effects were similar between study groups and none required treatment, including among the subset of 39 women, who received misoprostol for both of its PPH indications.

Conclusions

While the study did not document a clinical benefit associated with misoprostol for treatment of PPH, study findings suggest that use of misoprostol for both prevention and treatment in the same birth as well as its use by lay level providers in home births does not result in any safety concerns.

Trial registration

This trial was registered with ClinicalTrials.gov, number NCT01508429 Registered on December 1, 2011.
Caloric restriction attenuates C57BL/6 J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure
Authors: Li Daochuan , Chen Shen , Li Qiong , Chen Liping , Zhang Haiyan , Li Huiyao , Yu Dianke , Zhang Rong , Niu Yujie , Lu Shaoyou , Ye Lizhu , Zeng Xiaowen , Dong Guanghui , Chen Rui , Aschner Michael , Zheng Yuxin , Chen Wen
Published: June 2020

Background

Caloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.

Results

Male C57BL/6 J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m3) of PM2.5. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.

Conclusion

These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.
Revisiting the public health implications of the United States–Mexico– Canada agreement
Authors: Adekola Tolulope Anthony
Published: June 2020

This commentary re-examines a recent article by Labonté et al on the recent changes to two relevant provisions relating to patent rights in the final version of the United-States-Mexico-Canada Agreement (USMCA). Although the USMCA’s final revised version does not add more pharmaceutical patent protection than those that already exist in the three trading partners, the agreement has done little to enhance access to generic medicines and biosimilars.
Prevalence of drug use, alcohol consumption, cigarette smoking and measure of socioeconomic-related inequalities of drug use among Iranian people: findings from a national survey
Authors: Moradinazar Mehdi , Najafi Farid , Jalilian Farzad , Pasdar Yahya , Hamzeh Behrooz , Shakiba Ebraim , Hajizadeh Mohammad , Haghdoost Ali Akbar , Malekzadeh Reza , Poustchi Hossein , Nasiri Marzeyeh , Okati-Aliabad Hassan , Saeedi Majid , Mansour-Ghanaei Fariborz , Farhang Sara , Safarpour Ali Reza , Maharlouei Najmeh , Farjam Mojtaba , Amini Saeed , Amini Mahin , Mohammadi Ali , Mirzaei-Alavijeh Mehdi
Published: June 2020

Background

Drug use can lead to several psychological, medical and social complications. The current study aimed to measure and decomposes socioeconomic-related inequalities in drug use among adults in Iran.

Methods

This was a cross-sectional study The PERSIAN Cohort is the largest and most important cohort among 18 distinct areas of Iran. This study was conducted on 130,570 adults 35 years and older. A structured questionnaire was applied to collect data. The concentration index (C) was used to quantify and decompose socioeconomic inequalities in drug use.

Results

The prevalence experience of drug use was 11.9%. The estimated C for drug use was − 0.021. The corresponding value of the C for women and men were − 0.171 and − 0.134, respectively. The negative values of the C suggest that drug use is more concentrated among the population with low socioeconomic status in Iran (p < 0.001). For women, socioeconomic status (SES) (26.37%), province residence (− 22.38%) and age (9.76%) had the most significant contribution to socioeconomic inequality in drug use, respectively. For men, SES (80.04%), smoking (32.04%) and alcohol consumption (− 12.37%) were the main contributors to socioeconomic inequality in drug use.

Conclusions

Our study indicated that drug use prevention programs in Iran should focus on socioeconomically disadvantaged population. Our finding could be useful for health policy maker to design and implement effective preventative programs to protect Iranian population against the drug use.
Improvement in functional gait parameters following corrective thoracolumbar surgery in children affected by Mucopolysaccharidosis 1 (Hurler syndrome)
Authors: Sundarapandian Rajkumar , Jones Simon , Broomfield Alexander , Hensman Pauline , Oxborrow Neil
Published: June 2020

Objective

Thoracolumbar kyphosis is a common indication for spinal surgery in children with Mucopolysaccharidosis. Functional outcome of spinal surgical intervention has never been published in patients with this rare disease. We present a cohort of patients with Mucopolysaccharidosis 1(Hurler syndrome) who underwent thoraco-lumbar spinal deformity correction and functional outcome assessed by pre-operative and post-operative gait analysis. This study represents the first attempt at presenting a functional assessment of surgical outcome in any Mucopolysaccharidosis subtype.

Methods

A retrospective analysis of prospectively collected data was carried out from 11 children diagnosed with this subtype of Mucopolysaccharidosis. All patients underwent thoracolumbar kyphosis correction between the years 2013 to 2016. Gait assessment was performed using GAITRite™ electronic walkway pre-operatively and post-operatively within 9 to 24 months from the index surgery. Walking distance, cadence and gait velocity were the three spatio-temporal parameters analysed. Wilcoxon signed rank test was used to analyse the data and P-Value ≤0.05 was deemed significant.

Results

There was a statistically significant improvement in walking distance in 9 out of 11 patient post-operatively with a mean increase of 232.06 cms (P = 0.05). There was marginal improvement in cadence by 6.33 steps/min post-operatively (P-value 0.79). Gait velocity also showed a marginal increase by 8.73 cms/sec post-operatively (P-value 0.32).

Conclusion

The results of our study suggest that correction of thoracolumbar kyphosis in children with Mucopolysaccharidosis 1 resulted in a significant improvement of walking distance with a trend towards improved gait in the other parameters. Post-operative change in cadence was not statistically significant suggesting that physiological maturation of gait had minimal effect in the specified post-operative assessment timeframe. This study emphasizes that outcomes of spinal surgery in children with Mucopolysaccharidosis 1 should be determined by functional measures aiming to maintain or improve quality of life.
Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis
Authors: Crisafulli Salvatore , Sultana Janet , Fontana Andrea , Salvo Francesco , Messina Sonia , Trifirò Gianluca
Published: June 2020

Background

Duchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. A recent systematic review and meta-analysis of global DMD epidemiology is not available. This study aimed to estimate the global overall and birth prevalence of DMD through an updated systematic review of the literature.

Methods

MEDLINE and EMBASE databases were searched for original research articles on the epidemiology of DMD from inception until 1st October 2019. Studies were included if they were original observational research articles written in English, reporting DMD prevalence and/or incidence along with the number of individuals of the underlying population. The quality of the studies was assessed using a STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist adapted for observational studies on rare diseases. To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using random-effects logistic models for overall and birth prevalence and within two different underlying populations (i.e. all individuals and in males only), separately. Heterogeneity was assessed using Cochran’s Q-test along with its derived measure of inconsistency I2.

Results

A total of 44 studies reporting the global epidemiology of DMD were included in the systematic review and only 40 were included in the meta-analysis. The pooled global DMD prevalence was 7.1 cases (95% CI: 5.0–10.1) per 100,000 males and 2.8 cases (95% CI: 1.6–4.6) per 100,000 in the general population, while the pooled global DMD birth prevalence was 19.8 (95% CI:16.6–23.6) per 100,000 live male births. A very high between-study heterogeneity was found for each epidemiological outcome and for all underlying populations (I2 > 90%). The test for funnel plot asymmetry suggested the absence of publication bias. Of the 44 studies included in this systematic review, 36 (81.8%) were assessed as being of medium and 8 (18.2%) of low quality, while no study was assessed as being of high quality.

Conclusions

Generating epidemiological evidence on DMD is fundamental to support public health decision-making. The high heterogeneity and the lack of high quality studies highlights the need to conduct better quality studies on rare diseases.
Utility of plasma Neurofilament light as a diagnostic and prognostic biomarker of the postural instability gait disorder motor subtype in early Parkinson’s disease
Authors: Ng Adeline Su Lyn , Tan Yi Jayne , Yong Alisa Cui Wen , Saffari Seyed Ehsan , Lu Zhonghao , Ng Ebonne Yulin , Ng Samuel Yong Ern , Chia Nicole Shuang Yu , Choi Xinyi , Heng Dede , Neo Shermyn , Xu Zheyu , Keong Nicole Chwee Har , Tay Kay Yaw , Au Wing Lok , Tan Louis Chew Seng , Tan Eng-King
Published: June 2020

Background

The main motor subtypes of Parkinson’s disease (PD) include tremor-dominant (TD) and postural instability gait disorder (PIGD), with varying disease course that warrant the development of biomarkers capable of predicting progression according to motor subtype. The PIGD subtype is associated with a poorer prognosis, hence identification of a biomarker associated with PIGD is clinically relevant. Neurofilament light (NfL) chain is a potential biomarker of disease severity in neurological disorders including PD. However, no study has investigated NfL and PD motor subtypes. Here, we aimed to investigate the diagnostic and prognostic utility of plasma NfL for PD motor subtypes in early Parkinson’s disease. Given the higher risk for cognitive and motor decline in PIGD, we hypothesized that plasma NfL is a potential biomarker for PIGD.

Methods

Plasma NfL was measured in 199 participants (149 PD and 50 healthy controls, HC) using an ultrasensitive single molecule array. Patients were classified into TD or PIGD based on MDS-UPDRS components. After 2 years, 115 patients were reassessed. Association between NfL and clinical measures in PIGD and TD at baseline and at 2-year follow-up were analysed.

Results

At baseline, plasma NfL levels were higher in PD than HC (8.8 ± 3.4 vs 16.2 ± 7.6 pg/ml, p < 0.0001), and differentiated PD from HC with a good diagnostic accuracy (AUC = 0.833, p < 0.001). At 2 years, NfL was higher in PIGD than TD (18.4 ± 14.5 vs 12.6 ± 4.4 pg/ml, p = 0.039). Within the PIGD group, higher NfL associated significantly with worse global cognition and UPDRS motor scores at baseline, and was able to predict motor and cognitive decline at a mean follow-up duration of 1.9 years, controlled for age, sex and disease duration.

Conclusions

In this longitudinal study, we demonstrated for the first time the potential utility of plasma NfL as a diagnostic and prognostic biomarker in PIGD even at early stages of PD. These important novel findings will require further confirmation in larger, longitudinal PD cohorts.
A survey of ivermectin resistance in Parascaris species infected foals in south-eastern Poland
Authors: Studzińska Maria Bernadeta , Sallé Guillaume , Roczeń-Karczmarz Monika , Szczepaniak Klaudiusz , Demkowska-Kutrzepa Marta , Tomczuk Krzysztof
Published: June 2020

Parascaris spp. are major gastro-intestinal nematodes that infect foals and can lead to respiratory symptoms, poor growth, and in some cases obstruction of the small intestine and death. Ivermectin resistance has been reported for Parascaris spp. in many countries. In Poland, the knowledge of the level of resistance against ivermectin in Parascaris spp. is limited. The aim of this study was to examine the efficacy of ivermectin against Parascaris spp. in foals from south-eastern Poland. Foals (n = 225 = reared in 7 stud farms) were treated orally with ivermectin paste. Faecal samples were collected from the rectum of each foal or from the environment straight after defaecation on 1 day prior and 2 weeks after deworming. A faecal egg count (FEC) was performed using the McMaster method with a minimum detection limit of 50 eggs/g. FEC reduction (FECR) was calculated using the Faecal Egg Count Reduction Test. The statistical analysis was limited to foals excreting more than 150 eggs/g before treatment and to stud farms with at least 6 foals excreting at or above this level. Confidence intervals were determined by 1000 bootstraps at farm level and the contribution of sex and age to FECR was quantified using a generalized equation estimation procedure. Parascaris spp. eggs were found in 40% of the foals. Following ivermectin treatment, Parascaris spp. eggs were identified in 28.4% of the foals. The mean estimated FECR ranged from 44% to 97% and average efficacy was 49.3%. FECR was more pronounced in older foals (P-values = 0. 003). The FECR was more pronounced in males than in females (P value = 0.028). This study is the first to indicate a reduced efficacy of ivermectin against Parascaris spp. in foals in Poland.
Long non-coding RNAs in ovarian granulosa cells
Authors: Tu Jiajie , Chen Yu , Li Zhe , Yang Huan , Chen He , Yu Zhiying
Published: June 2020

Granulosa cells (GCs) are somatic cells surrounding oocytes within follicles and are essential for folliculogenesis. Pathological changes in GCs are found in several ovarian disorders. Recent reports have indicated that long non-coding RNAs (lncRNAs), which modulate gene expression via multiple mechanisms, are key regulators of the normal development of GCs, follicles, and ovaries. In addition, accumulating evidence has suggested that lncRNAs can be utilized as biomarkers for the diagnosis and prognosis of GC-related diseases, such as polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Therefore, lncRNAs not only play a role in GCs that are involved in normal folliculogenesis, but they may also be considered as potential candidate biomarkers and therapeutic targets in GCs under pathological conditions. In the future, a detailed investigation of the in vivo delivery or targeting of lncRNAs and large-cohort-validation of the clinical applicability of lncRNAs is required.
Increased risk for uterine cancer among first-degree relatives to Swedish gastric cancer patients
Authors: Samola Winnberg Johanna , Rudd Eva , Keränen Anne , Lagerstedt-Robinson Kristina , Lindblom Annika , Nilsson Magnus , Lindblad Mats , Sjödahl Krister
Published: June 2020

Purpose

In order to further understand genetically predisposing factors of gastric cancer, a retrospective study on 107 patients with gastric cancer was conducted. The family history of cancer cases was registered, in search of associations between gastric cancer and other cancer types.

Materials and methods

Within Stockholm County in Sweden, all patients previously diagnosed with gastric cancer and still alive were invited to participate in the study. Patients were asked to complete a questionnaire about their gastric cancer diagnosis and if any cancers had occurred in their family. A blood sample for DNA extraction was collected. The proportions of different cancer types in the relatives of the patients were compared to the general Swedish population in 1970 and 2010.

Results

Among first- and second-degree relatives to the index patients with gastric cancer, the frequency of uterine cancer as well as gastric cancer was significantly overrepresented compared to the general population in Sweden. The frequency of breast cancer was significantly lower.

Conclusions

There seems to be an increased risk of both gastric cancer and uterine cancer in the families of gastric cancer survivors, indicating a possible hereditary connection between these two cancer types.
In-hospital airway management of COVID-19 patients
Authors: Sullivan Elise H. , Gibson Lauren E. , Berra Lorenzo , Chang Marvin G. , Bittner Edward A.
Published: June 2020

Those involved in the airway management of COVID-19 patients are particularly at risk. Here, we describe a practical, stepwise protocol for safe in-hospital airway management in patients with suspected or confirmed COVID-19 infection.
Pragmatic cluster randomized trial to evaluate effectiveness and implementation of enhanced EHR-facilitated cancer symptom control (E2C2)
Authors: Finney Rutten Lila J. , Ruddy Kathryn J. , Chlan Linda L. , Griffin Joan M. , Herrin Jeph , Leppin Aaron L. , Pachman Deirdre R. , Ridgeway Jennifer L. , Rahman Parvez A. , Storlie Curtis B. , Wilson Patrick M. , Cheville Andrea L.
Published: June 2020

Background

The prevalence of inadequate symptom control among cancer patients is quite high despite the availability of definitive care guidelines and accurate and efficient assessment tools.

Methods

We will conduct a hybrid type 2 stepped wedge pragmatic cluster randomized clinical trial to evaluate a guideline-informed enhanced, electronic health record (EHR)-facilitated cancer symptom control (E2C2) care model. Teams of clinicians at five hospitals that care for patients with various cancers will be randomly assigned in steps to the E2C2 intervention. The E2C2 intervention will have two levels of care: level 1 will offer low-touch, automated self-management support for patients reporting moderate sleep disturbance, pain, anxiety, depression, and energy deficit symptoms or limitations in physical function (or both). Level 2 will offer nurse-managed collaborative care for patients reporting more intense (severe) symptoms or functional limitations (or both). By surveying and interviewing clinical staff, we will also evaluate whether the use of a multifaceted, evidence-based implementation strategy to support adoption and use of the E2C2 technologies improves patient and clinical outcomes. Finally, we will conduct a mixed methods evaluation to identify disparities in the adoption and implementation of the E2C2 intervention among elderly and rural-dwelling patients with cancer.

Discussion

The E2C2 intervention offers a pragmatic, scalable approach to delivering guideline-based symptom and function management for cancer patients. Since discrete EHR-imbedded algorithms drive defining aspects of the intervention, the approach can be efficiently disseminated and updated by specifying and modifying these centralized EHR algorithms.

Trial registration

ClinicalTrials.gov, NCT03892967. Registered on 25 March 2019.
Evidencing the impact of cancer trials: insights from the 2014 UK Research Excellence Framework
Authors: Hanna Catherine R. , Gatting Lauren P. , Boyd Kathleen Anne , Robb Kathryn A. , Jones Rob J.
Published: June 2020

Introduction

An impactful clinical trial will have real-life benefits for patients and society beyond the academic environment. This study analyses case studies of cancer trials to understand how impact is evidenced for cancer trials and how impact evaluation can be more routinely adopted and improved.

Methods

The United Kingdom (UK) Government allocates research funding to higher-education institutions based on an assessment of the institutions’ previous research efforts, in an exercise known as the Research Excellence Framework (REF). In addition to each institution’s journal publications and research environment, for the first time in 2014, allocation of funding was also dependent on an evaluation of the wider, societal impact of research conducted. In the REF2014, impact assessment was performed by evaluation of impact case studies. In this study, case studies (n = 6637) submitted by institutions for the REF2014 were accessed and those focussing on cancer trials were identified. Manual content analysis was then used to assess the characteristics of the cancer trials discussed in the case studies, the impact described and the methods used by institutions to demonstrate impact.

Results

Forty-six case studies describing 106 individual cancer trials were identified. The majority were phase III randomised controlled trials and those recruiting patients with breast cancer. A list of indicators of cancer trial impact was generated using the previous literature and developed inductively using these case studies. The most common impact from a cancer trial identified in the case studies was on policy, in particular citation of trial findings in clinical guidelines. Impact on health outcomes and the economy were less frequent and health outcomes were often predicted rather than evidenced. There were few descriptions identified of trialists making efforts to maximise trial impact.

Discussion

Cancer trial impact narratives for the next REF assessment exercise in 2021 can be improved by evidencing actual rather than predicted Impact, with a clearer identification of the beneficiaries of cancer trials and the processes through which trial results are used. Clarification of the individuals responsible for performing impact evaluations of cancer trials and the provision of resources to do so needs to be addressed if impact evaluation is to be sustainable.
Efficacy of Parent-Infant-Psychotherapy with mothers with postpartum mental disorder: study protocol of the randomized controlled trial as part of the SKKIPPI project
Authors: Mattheß J. , Eckert M. , Richter K. , Koch G. , Reinhold T. , Vienhues P. , Berghöfer A. , Roll S. , Keil T. , Schlensog-Schuster F. , von Klitzing K. , Ludwig-Körner C. , Kuchinke L.
Published: June 2020

Background

After the birth of a child, many mothers and fathers experience postpartum mental disorders like depression, anxiety, obsessive-compulsive disorder, stress or other illnesses. This endangers the establishment of a secure attachment between the children and their primary caregivers. Early problems in parent-child interaction can have adverse long-term effects on the family and the child’s well-being. In order to prevent a transgenerational transmission of mental disorders, it is necessary to evaluate psychotherapeutic interventions that target psychologically burdened parents of infants or toddlers. The aim of this trial is to investigate the efficacy of Parent-Infant-Psychotherapy (PIP) for mothers with postpartum mental disorder and their infants (0–12 months).

Methods/design

In this open, randomized controlled intervention trial 180 mother-infant-dyads will be included and randomly allocated to 12 sessions of PIP or care as usual. The interventions take place either in inpatient adult psychiatric departments or in outpatient settings with home visits. The primary outcome is the change in maternal sensitivity assessed by the Sensitivity subscale of the Emotional Availability Scale (EAS) through videotaped dyadic play-interactions after 6 weeks. Secondary outcomes are maternal psychopathology, stress, parental reflective functioning, infant development and attachment after 6 weeks and 12 months. In addition, maternal attachment (AAI) and reflective functioning (AAI) will be analyzed as potential moderators, and resource usage in the German health system as well as associated costs will be evaluated.

Discussion

There is increasing demand for well-controlled studies on psychotherapeutic interventions in the postpartum period that do not only focus on particular risk groups. This randomized controlled trial (RCT) represents one of the first studies to investigate the efficacy of PIP in inpatient psychiatric departments and outpatient care centers in Germany. The results will fill knowledge gaps on the factors contributing to symptom reduction in postpartum mental disorders and improvements in mother-child relationships and help in developing preventive and therapeutic strategies for the fragmented German health care system.

Trial registration

German Register for Clinical Trials, ID: DRKS00016353.
Acetylcholinesterase (ace-1R) target site mutation G119S and resistance to carbamates in Anopheles gambiae (sensu lato) populations from Mali
Authors: Keïta Moussa , Kané Fousseyni , Thiero Oumar , Traoré Boissé , Zeukeng Francis , Sodio Ambiélè Bernard , Traoré Sekou Fantamady , Djouaka Rousseau , Doumbia Seydou , Sogoba Nafomon
Published: June 2020

Background

The long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are major malaria vector control strategies in Mali. The success of control strategies depends on a better understanding of the status of malaria vectors with respect to the insecticides used. In this study we evaluate the level of resistance of Anopheles gambiae (sensu lato) to bendiocarb and the molecular mechanism that underlies it.

Methods

Larvae of An. gambiae (s.l.) were collected from breeding habitats encountered in the three study sites and bioassayed with bendiocarb. The ace-1 target site substitution G119S was genotyped using a TaqMan assay.

Results

The three species of the An. gambiae complex in Mali, i.e. An. arabiensis, An. coluzzii and An. gambiae (s.s.) were found in sympatry in the three surveyed localities with different frequencies. We observed a resistance and suspicious resistance of the three species to bendiocarb with a mortality rate ranging from 37% to 86%. The allelic frequency of the G119S mutation was higher in An. gambiae (s.s.) compared to the other two species; 42.86%, 25.61% and 16.67% respectively in Dangassa, Koula, and Karadié. The allelic frequency of G119S in An. coluzzii ranged from 4.5% to 8.33% and from 1.43% to 21.15% for An. arabiensis. After exposure to bendiocarb, the G119S mutation was found only in survivors. The survival of Anopheles gambiae (s.l) populations from the three surveyed localities was associated with the presence of the mutation.

Conclusions

The study highlights the implication of G119S mutation in bendiocarb resistance in An. gambiae (s.s.), An. arabiensis and An. coluzzii populations from the three surveyed localities.
Glucose transporter GLUT1 influences Plasmodium berghei infection in Anopheles stephensi
Authors: Wang Mengfei , Wang Jingwen
Published: June 2020

Background

Sugar-feeding provides energy for mosquitoes. Facilitated glucose transporters (GLUTs) are responsible for the uptake of glucose in animals. However, knowledge of GLUTs function in Anopheles spp. is limited.

Methods

Phylogenetic analysis of GLUTs in Anopheles stephensi was performed by the maximum likelihood and Bayesian inference methods. The spatial and temporal expression patterns of four Asteglut genes were analyzed by qPCR. The function of Asteglut1 was examined using a dsRNA-mediated RNA interference method. Transcriptome analysis was used to investigate the global influence of Asteglut1 on mosquito physiology.

Results

We identified 4 glut genes, Asteglut1, Asteglutx, Asteglut3 and Asteglut4 in An. stephensi. Asteglut1, Asteglut3 and Asteglut4 were mainly expressed in the midgut. Plasmodium berghei infection differentially regulated the expression of Asteglut genes with significant downregulation of Asteglut1 and Asteglut4, while upregulation of Asteglutx. Only knocking-down Asteglut1 facilitated Plasmodium berghei infection in An. stephensi. This might be due to the accumulation of glucose prior to blood-feeding in dsAsteglut1-treated mosquitoes. Our transcriptome analysis revealed that knockdown of Asteglut1 differentially regulated expression of genes associated with multiple functional clusters, especially those related to detoxification and immunity. The dysregulation of multiple pathways might contribute to the increased P. berghei infection.

Conclusions

Our study shows that Asteglut1 participates in defense against P. berghei in An. stephensi. The regulation of Asteglut1 on vector competence might through modulating multiple biological processes, such as detoxification and immunity.
On the validity of “Candidatus Dirofilaria hongkongensis” and on the use of the provisional status Candidatus in zoological nomenclature
Authors: Dantas-Torres Filipe , Otranto Domenico
Published: June 2020

The fast development of molecular taxonomy is impacting our knowledge of the world parasite diversity at an unprecedented level. A number of operational taxonomic units have been uncovered and new species described. However, it is not always that new parasite species are being described in compliance with the International Code of Zoological Nomenclature. This is the case of “Candidatus Dirofilaria hongkongensis”, a nematode found in dogs, jackals and humans in Hong Kong and parts of India. This name has been proposed without a formal description and without the designation of a holotype, and therefore is an unavailable name. Finally, we argue that using the provisional status Candidatus in zoological nomenclature is inappropriate, considering this term is not considered in the International Code of Zoological Nomenclature.
Ezh2-mediated epigenetic modification is required for allogeneic T cell-induced lupus disease
Authors: Zhen Yuxuan , Smith Roger D. , Finkelman Fred D. , Shao Wen-Hai
Published: June 2020

Background

The mechanisms involved in the pathogenesis of autoimmune disorders, including systemic lupus erythematosus (SLE), have not been fully elucidated. Some of these mechanisms involve epigenetic regulation of gene expression. The histone methyltransferase Ezh2 contributes to epigenetic regulation of gene expression, is highly expressed in germinal center (GC) B cells and follicular T helper (TFH) cells, and may be involved in lupus pathogenesis.

Methods

The murine bm12 model of lupus-like chronic graft versus host disease (cGVHD) was induced by intra-peritoneal injection of negatively isolated allogeneic CD4+ T cells. Lupus-like disease development was monitored by ELISA determination of serum anti-dsDNA and anti-chromatin antibody titers. Immune cell activation and Ezh2 expression were evaluated by flow cytometry and Western blotting.

Results

Decreased autoantibody production and GC formation are observed when Ezh2-deficient CD4+ T cells are used instead of wild-type (WT) to induce cGVHD and when mice that receive allogeneic WT donor T cells to induce cGVHD are treated with GSK503, an Ezh2-specific inhibitor. In the bm12 cGVHD model, WT donor T cells are normally fully activated 1 week after infusion into an allogeneic host, exhibit a TFH cell (PD-1hi/CXCR5hi) phenotype with upregulated Ezh2, and activate B cells to form germinal centers (GCs). In contrast, Ezh2-deficient donor T cells generate fewer TFH cells that fail to activate B cells or promote GC formation. Despite similar T-independent, LPS-induced B cell responses, OVA-immunized CD4.Ezh2-KO mice had a skewed low-affinity IgM phenotype in comparison to similarly treated WT mice. In addition, early after OVA immunization, more CD4+ T cells from B6.CD4.Ezh2-KO mice had a CD44lo/CD62Llo phenotype, which suggests arrested or delayed activation, than CD4+ T cells from ovalbumin-immunized B6.WT mice.

Conclusion

Ezh2 gene deletion or pharmacological Ezh2 inhibition suppresses autoantibody production and GC formation in bm12 lupus-like cGVHD and decreases affinity maturation and isotype switching in response to immunization with a T cell-dependent antigen. Ezh2 inhibition may be useful for the treatment of lupus and other autoimmune disorders.
The involving progress of MSCs based therapy in atherosclerosis
Authors: Lin Ying , Zhu Wei , Chen Xiaomin
Published: June 2020

Atherosclerosis is a chronic progressive vascular inflammation characterized by lipid deposition and plaque formation, for which vascular cell dysfunction and impaired immune responses are involved. Up to now, lipid-lowering drugs remain the main therapy for treating atherosclerosis; however, the surgical or interventional therapy is often applied, and yet, morbidity and mortality of such cardiovascular disease remain high worldwide. Over the past decades, an anti-inflammatory approach has become an important therapeutic target for dealing with atherosclerosis, as altered immune responses have been regarded as an essential player in the pathological process of vascular abnormality induced by hyperlipidemia. Interestingly, mesenchymal stem cells, one type of stem cells with the capabilities of self-renewal and multi-potential, have demonstrated their unique immunomodulatory function in the various pathological process, especially in atherosclerosis. While some controversies remain regarding their therapeutic efficacy and working mechanisms, our present review aims to summarize the current research progress on stem cell-based therapy, focusing on its immunomodulatory effects on the pathogenesis of atherosclerosis and how endothelial cells, smooth muscle cells, and other immune cells are regulated by MSC-based therapy.
Fasciola hepatica coinfection modifies the morphological and immunological features of Echinococcus granulosus cysts in cattle
Authors: Hidalgo Christian , Stoore Caroll , Hernández Marcela , Paredes Rodolfo
Published: June 2020

Polyparasitism occurs when animals harbour multiple parasites concomitantly. It is a common occurrence but is generally understudied in wild and domestic animals. Fasciola hepatica and Echinococcus granulosus, which are helminths of ungulates, frequently coinfect cattle. The effects of this particular type of polyparasitism are not well documented. The metacestode of Echinococcus granulosus is surrounded by the adventitial layer, which constitutes the host immune response to the parasite. This layer in cattle is produced by a granulomatous reaction and is involved in echinococcal cyst (EC) fertility. Due to the systemic immune-modulating abilities of Fasciola hepatica, coinfection possibly generates a favourable environment for EC growth. A total of 203 Echinococcus granulosus sensu stricto cysts were found in 82 cattle, of which 42 ECs were found in 31 animals coinfected with Fasciola hepatica. The overall infection intensity was 3 cysts per animal. Coinfection with Fasciola hepatica decreased the mean infection intensity to 1.4 cysts per animal. Regarding EC size, coinfection resulted in smaller ECs (15.91 vs 22.09 mm), especially for infertile lung cysts. The adventitial layer of ECs in coinfected animals lacked lymphoid follicles and palisading macrophages, which are generally hallmarks of the granulomatous immune response. The ECs in coinfected animals had organized laminated layers, whereas those in animals without coinfection did not. Although coinfection was not statistically associated with EC fertility, we did not find fertile cysts in the livers of coinfected animals. We concluded that coinfection with Fasciola hepatica and Echinococcus granulosus has a detrimental effect on ECs, particularly infertile cysts.
Identification, cloning and expression patterns of the genes related to phosphate solubilization in Burkholderia multivorans WS-FJ9 under different soluble phosphate levels
Authors: Liu Yu-Qing , Wang Ya-Hui , Kong Wei-Liang , Liu Wan-Hui , Xie Xing-Li , Wu Xiao-Qin
Published: June 2020

As important plant growth-promoting rhizobacteria, phosphate-solubilizing bacteria (PSB) fix nitrogen, dissolve potassium, promote growth, improve the soil micro-environment, and enhance soil fertility. A high-efficiency PSB strain from the pine tree rhizosphere, Burkholderia multivorans WS-FJ9, was screened in our laboratory. In this study, using a Bio Screener fully automatic microbial growth curve meter to determine the growth of the WS-FJ9 strain in phosphate-removing medium, the growth and mineral phosphate solubilization of WS-FJ9 were measured by Mo-Sb colorimetry and organophosphate-solubilization plate assays. Second-generation sequencing technology was used to obtain genomic information and to analyze possible phosphate decomposition genes. The related expression levels of these genes under different soluble phosphate levels were determined by quantitative real-time PCR. The results showed that WS-FJ9 had strong adaptability and capacity for mineral phosphate solubilization at low soluble phosphate levels, which is characterized by its low soluble phosphate induction and high soluble phosphate inhibition. The amount of solubilized mineral phosphate could exceed 140 mg/L. The total length of the WS-FJ9 genome was 7,497,552 bp after splicing, and the GC content was 67.37%. Eight phosphate-related genes were selected to determine their expression patterns at different soluble phosphate levels. Among them, AP-2, GspE and GspF were only related to organic phosphate, HlyB was only related to inorganic phosphate, and PhoR, PhoA, AP-1 and AP-3 were related to both. The WS-FJ9 strain utilizes multiple pathways for mineral phosphate solubilization, and the solubilization processes of different phosphate sources are interrelated and independent, indicating that the WS-FJ9 strain can adapt to different phosphate source environments and has good potential for future applications.
Effects on development and microbial community of shrimp Litopenaeus vannamei larvae with probiotics treatment
Authors: Wang Ruixuan , Guo Zihan , Tang Yapeng , Kuang Jiawei , Duan Yafei , Lin Heizhao , Jiang Shigui , Shu Hu , Huang Jianhua
Published: June 2020

Shrimp production is the second ranked of the most-traded production in these decades and the whiteleg shrimp Litopenaeus vannamei is the sixth most cultured species. Probiotics are alternative strategy for the promotion of growth and prevention of diseases in aquaculture. To confirm the effects of the probiotics on development and microbial community of L. vannamei larvae during different development stages, five kinds of probiotics (108 ~ 109 CFU/g) were added into the rearing environment of shrimp larvae, and the effects of probiotics on bacterial community and water quality, larval growth and immune index were determined from nauplius larval stage to post larval stage. Results suggested that probiotics treated groups showed larger survival rate than the control groups from Z1 stage to P5 stage. Lactobacillus could improve the larvae’s survival ability, especially in the larval stages M2, M3, P1, P5 stage. It was confirmed that probiotics could promote the growth and development of shrimp larvae and prevent the incomplete molting in their growing process, particularly for EM-treated group. Results suggested that all the probiotics-treated groups had shown significant decreasing trend in the quantity of vibrios, except for the SA-treated group. And different probiotics could inhibit vibrios during different life periods. Among these probiotics, LA, EM and PB had shown the best effects, including improving survival rate of the larvae, promoting the larval metamorphosis, reducing the quantity of vibrios and NH4-N and NO2-N levels, and increasing bacterial diversity.
Channel-bonding CMOS transceiver for 100 Gbps wireless point-to-point links
Authors: Gonzalez-Jimenez José Luis , Dehos Cédric , Cassiau Nicolas , Siligaris Alexandre , Clemente Antonio , D’Errico Rafaelle , Savin Valentin , Durand Yves , De Domenico Antonio , Noguet Dominique
Published: June 2020

5G systems and networks are expected to provide unprecedented data-rate to final users and services, in combination with increased coverage and density. The traffic generated at the edges of the network should be hauled through high capacity data-conveyors. Extremely high data-rate links able to provide optical-fiber like performance in the order of 100 Gbps are required to reduce the cost and increase the flexibility of the network infrastructure deployment. This paper presents a full transceiver architecture based on a channel-bonding radio-frequency front-end operating at millimeter-wave frequencies and digital baseband processing units able to provide such data-rates with a feasible implementation in low-cost CMOS technologies. The baseband section of the receiver includes digital compensation algorithms that allow to cope with some of the radio front-end impairments. The main functionalities of the proposed transceiver architecture are validated in hardware.