bluuebunny/crossref_metadata_2025 huggingface dataset:
PES1 is a critical component of telomerase assembly and regulates cellular senescence
Authors: Cheng Long , Yuan Bin , Ying Sunyang , Niu Chang , Mai Hongxu , Guan Xin , Yang Xiaohui , Teng Yan , Lin Jing , Huang Junjian , Jin Rui , Wu Jun , Liu Bo , Chang Shaohong , Wang Enqun , Zhang Chunxia , Hou Ning , Cheng Xuan , Xu Danyang , Yang Xiao , Gao Shan , Ye Qinong
Published: May 2019

PES1 is a new component of telomerase assembly that regulates telomerase activity, telomere length, and cellular senescence.
Multiplexed single-cell RNA-seq via transient barcoding for simultaneous expression profiling of various drug perturbations
Authors: Shin Dongju , Lee Wookjae , Lee Ji Hyun , Bang Duhee
Published: May 2019

The authors developed a method for analyzing single cells under various conditions by tagging cells with small fragments of DNA.
Macrophage centripetal migration drives spontaneous healing process after spinal cord injury
Authors: Kobayakawa Kazu , Ohkawa Yasuyuki , Yoshizaki Shingo , Tamaru Tetsuya , Saito Takeyuki , Kijima Ken , Yokota Kazuya , Hara Masamitsu , Kubota Kensuke , Matsumoto Yoshihiro , Harimaya Katsumi , Ozato Keiko , Masuda Takahiro , Tsuda Makoto , Tamura Tomohiko , Inoue Kazuhide , Edgerton V. Reggie , Iwamoto Yukihide , Nakashima Yasuharu , Okada Seiji
Published: May 2019

Migration of macrophages via IRF8 toward a core lesion is important for the spontaneous recovery after spinal cord injury.
ALBA protein complex reads genic R-loops to maintain genome stability in
Arabidopsis
Authors: Yuan Wei , Zhou Jincong , Tong Jinjin , Zhuo Wanqing , Wang Lishuan , Li Yan , Sun Qianwen , Qian Weiqiang
Published: May 2019

AtALBA1 and AtALBA2 are genic R-loop readers.
Fifteen-minute consultation: Pharmacogenomics: a guide for busy clinicians
Authors: Parry Christopher Mark , Hawcutt Daniel
Published: May 2019

The ultimate goal of pharmacogenomics is to understand how the effects of interindividual genetic variation impact on the response of patients to treatments and in turn optimise those treatments while minimising potential side effects. This review article provides a brief overview of pharmacogenomics, focusing on the methods used to understand how genes of interest are identified, how pharmacogenomics is currently used within paediatric clinical practice within the UK, potential areas for future use and some of the caveats specific to paediatric medicine.
Anterior interosseous nerve palsy as a result of prolonged shoulder immobilisation
Authors: Murphy Evelyn Patricia , Fenelon Christopher , Alexander Michael , Quinlan John
Published: May 2019

This is a rare case of an anterior interosseous nerve (AIN) palsy in a patient as a result of a prolonged period of shoulder immobilisation. The patient had an open reduction internal fixation of a midshaft clavicle fracture. They subsequently underwent removal of metal due to symptomatic prominence of the metal work. The patient was in a shoulder immobiliser for a period of 5 months in total. They developed progressive AIN palsy as a result of a positional compression due to prolonged wearing of a shoulder immobiliser. This resolved with conservative management and careful observation.
Malignant deep brain stimulator withdrawal syndrome
Authors: Azar Jehad , Elinav Hila , Safadi Rifaat , Soliman Mona
Published: May 2019

Parkinsonism-hyperpyrexia syndrome (PHS) is a neurologic potentially fatal emergency that mimics neuroleptic malignant syndrome. It commonly presents as systemic inflammatory response syndrome, acute onset worsening of muscular rigidity, autonomic instability, hyperpyrexia, confusion, diaphoresis and high creatine phosphokinase. The most common trigger for PHS is reduction or withdrawal of anti-Parkinson’s medications, especially levodopa. It was also reported in a few cases following deep brain stimulation of the subthalamic nucleus surgery shortly after anti-Parkinson’s medications were discontinued. Rare causes of PHS include deep brain stimulator (DBS) malfunction due to battery depletion. To the best of our knowledge, PHS following DBS battery depletion was reported only in three occasions. Here, we report a case of PHS due to DBS battery depletion presented as sepsis and was successfully treated with the administration of dopamine agonists, intravenous fluids and changing the DBS battery.
Autoimmune necrotizing myopathy after statin discontinuation
Authors: Abid Haisam , Watthanasuntorn Kanramon , Bischof Edward
Published: May 2019

We report a case of autoimmune necrotizing myopathy related to statin use in a 70-year-old woman who came to the hospital because of progressive lower extremity weakness. Laboratory, electromyography and muscle biopsy results were consistent with autoimmune necrotising myopathy. The patient was treated with intravenous immunoglobulin with improvement in muscle strength.
Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline
Authors: Bekkering G E , Agoritsas T , Lytvyn L , Heen A F , Feller M , Moutzouri E , Abdulazeem H , Aertgeerts B , Beecher D , Brito J P , Farhoumand P D , Singh Ospina N , Rodondi N , van Driel M , Wallace E , Snel M , Okwen P M , Siemieniuk R , Vandvik P O , Kuijpers T , Vermandere M
Published: May 2019

Clinical question

What are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice.

Current practice

Current guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing.

Recommendation

The guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old).

How this guideline was created

A guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach.

The evidence

The systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years’ follow-up.

Understanding the recommendation

The panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC (https://app.magicapp.org/) to support shared decisions and adaptation of this guideline.
Taking stock of cost-effectiveness analysis of healthcare in China
Authors: Butt Thomas , Liu Gordon G , Kim David D , Neumann Peter J
Published: May 2019

Introduction

Cost-effectiveness analysis (CEA) is playing an increasingly important role in informing healthcare decision-making in China. This study aims to review the published literature on CEA in mainland China and describe its characteristics and evolution. We provide recommendations on the future direction of CEA as a methodology and as a tool to support healthcare decision-making in China.

Methods

English-language cost-per-quality-adjusted life-year (QALY) and cost-per-disability-adjusted life-year (DALY) publications relating to mainland China were reviewed using the Tufts Medical Center Cost-Effectiveness Analysis Registry and Global Health Cost-Effectiveness Analysis Registry through 2017. Study features were summarised using descriptive statistics. Changes in study methodology over time were analysed by trend test, and study characteristics influencing the incremental cost-effectiveness ratio (ICER) of cost-per-QALY studies were investigated using logistic regression.

Results

170 studies were identified reporting CEA for mainland China (cost/QALY=125, cost/DALY=45) since 1998. The number and quality of studies has increased over the past two decades, with significantly more cost-per-QALY studies compared with cost-per-DALY studies (p<0.0001) and more studies with authors affiliated with Chinese institutions (p=0.0002). The average quality score was 5.04 out of 7 for cost-per-QALY and 4.70 for cost-per-DALY studies based on Registry reviewers’ subjective assessment of overall quality (methods, assumptions and reporting practices). The median ICER reported for interventions for oncology patients was higher (US$26 694 per QALY) than the median ICER reported for all interventions (US$11 503 per QALY). Oncology interventions were associated with the likelihood of reporting higher ICERs than the median ICER (p=0.003).

Conclusion

The number of English-language published CEA studies relating to China has grown rapidly over the past 20 years. In terms of quality, the China studies compare favourably with international studies, although they remain a small proportion of studies globally.
Acute and long-term clinical, neuropsychological and return-to-work sequelae following electrical injury: a retrospective cohort study
Authors: Radulovic Nada , Mason Stephanie A , Rehou Sarah , Godleski Matthew , Jeschke Marc G
Published: May 2019

Objective

To determine acute and long-term clinical, neuropsychological, and return-to-work (RTW) effects of electrical injuries (EIs). This study aims to further contrast sequelae between low-voltage and high-voltage injuries (LVIs and HVIs). We hypothesise that all EIs will result in substantial adverse effects during both phases of management, with HVIs contributing to greater rates of sequelae.

Design

Retrospective cohort study evaluating EI admissions between 1998 and 2015.

Setting

Provincial burn centre and rehabilitation hospital specialising in EI management.

Participants

All EI admissions were reviewed for acute clinical outcomes (n=207). For long-term outcomes, rehabilitation patients, who were referred from the burn centre (n=63) or other burn units across the province (n=65), were screened for inclusion. Six patients were excluded due to pre-existing psychiatric conditions. This cohort (n=122) was assessed for long-term outcomes. Median time to first and last follow-up were 201 (68–766) and 980 (391–1409) days, respectively.

Outcome measures

Acute and long-term clinical, neuropsychological and RTW sequelae.

Results

Acute clinical complications included infections (14%) and amputations (13%). HVIs resulted in greater rates of these complications, including compartment syndrome (16% vs 4%, p=0.007) and rhabdomyolysis (12% vs 0%, p<0.001). Rates of acute neuropsychological sequelae were similar between voltage groups. Long-term outcomes were dominated by insomnia (68%), anxiety (62%), post-traumatic stress disorder (33%) and major depressive disorder (25%). Sleep difficulties (67%) were common following HVIs, while the LVI group most frequently experienced sleep difficulties (70%) and anxiety (70%). Ninety work-related EIs were available for RTW analysis. Sixty-one per cent returned to their preinjury employment and 19% were unable to return to any form of work. RTW rates were similar when compared between voltage groups.

Conclusions

This is the first investigation to determine acute and long-term patient outcomes post-EI as a continuum. Findings highlight substantial rates of neuropsychological and social sequelae, regardless of voltage. Specialised and individualised early interventions, including screening for mental health concerns, are imperative to improvingoutcomes of EI patients.
Kanuka honey versus aciclovir for the topical treatment of herpes simplex labialis: a randomised controlled trial
Authors: Semprini Alex , Singer Joseph , Braithwaite Irene , Shortt Nick , Thayabaran Darmiga , McConnell Melanie , Weatherall Mark , Beasley Richard
Published: May 2019

Objective

To compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis.

Design

Prospective parallel randomised controlled open-label superiority trial.

Setting

76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017.

Participants

952 adults randomised within the first 72 hours of a herpes simplex labialis episode.

Interventions

Random assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily.

Outcome measures

The primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability.

Results

Primary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported.

Conclusion

There was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis.

Trial registration number

ACTRN12615000648527;Post-results
Perspectives of time: a qualitative study of the experiences of parents of critically ill newborns in the neonatal nursery in North Queensland interviewed several years after the admission
Authors: Ireland Susan , Ray Robin A , Larkins Sarah , Woodward Lynn
Published: May 2019

Design

A qualitative study informed by grounded theory principles to explore the experiences of parents who had extremely preterm or babies with antenatally diagnosed life-threatening diagnoses who were cared for in a regional tertiary neonatal unit. The study was conducted when the child was old enough to be diagnosed with long-term neurodevelopmental or medical sequelae.

Setting

North Queensland is a large area in Eastern Australia of 500 000 km2, which is served by one tertiary neonatal unit.

Participants

Seventeen families representing 21 extremely preterm babies and one baby with congenital malformations who was not expected to survive prior to delivery (but did) were interviewed using grounded theory principles. Interviews were coded and themes derived.

Results

Parents who recollect their neonatal experiences from 3 to 7 years after the baby was cared for in the neonatal intensive care described negative themes of grief and loss, guilt and disempowerment. Positive enhancers of care included parental strengths, religion and culture, family supports and neonatal unit practices. Novel findings included that prior pregnancy loss and infertility formed part of the narrative for parents, and hope was engendered by religion for parents who did not usually have a religious faith.

Conclusions

An understanding of both the negative aspects of neonatal care and the positive enhancers is necessary to improve the neonatal experience for parents. Parents are able to contextualise their previous neonatal experiences within both the long-term outcome for the child and their own life history.
Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial
Authors: de Boer Nadine L , van Kooten Job P , Burger Jacobus W A , Verhoef Cornelis , Aerts Joachim G J V , Madsen Eva V E
Published: May 2019

Introduction

Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.

Methods and analysis

The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma. Intervention: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.

Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.

Ethics and dissemination

Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.

Trial registration number

NTR7060. EudraCT: 2017-000897-12; Pre-Results.
Assessing the appropriateness of the management of upper respiratory tract infection in Australian children: a population-based sample survey
Authors: Long Janet C , Williams Helena M , Jani Shefali , Arnolda Gaston , Ting Hsuen P , Molloy Charlotte J , Hibbert Peter D , Churruca Kate , Ellis Louise A , Braithwaite Jeffrey
Published: May 2019

Objective

To assess the proportion of Australian children aged 0–15 years that received care in line with clinical practice guidelines (CPGs) for upper respiratory tract infections (URTIs).

Design

Retrospective medical record review using a multistage sampling strategy.

Setting

General practices, hospital emergency departments and hospital inpatient service providers in three Australian states.

Participants

Children aged up to 15 years who received care for URTI in 2012 and 2013.

Primary and secondary outcome measures

The primary assessment was estimated adherence with 14 indicators of appropriate care as documented in medical records. Indicators were extracted from national and international CPGs and ratified by experts. Secondary assessment was adherence to two bundles of indicators (diagnostic symptoms and medical history taking), where all indicators must be adherent for the bundle to be scored as adherent.

Results

There were 1653 children with one or more assessments of URTI care to CPG adherence. Over half of the children were under 3 years of age, with roughly equal numbers of males and females. Three indicators had fewer than 25 visits so were not reported. Overall adherence ranged from 0.5% for ‘documented advice around antibiotics’ to 88.3% for ‘documentation of medical history’. Adherence with Bundle A (documentation of all three definitive symptoms) was 43.1% (95% CI 32.8% to 54.0%) and Bundle B (documentation of all four indicators of medical history) was 30.2% (95% CI 20.9% to 40.9%).

Conclusions

URTIs in children are common, usually self-limiting, conditions that are allocated considerable resources. The results suggest that there may be a need for more thorough holistic assessment of the patient and improved documentation. Since inappropriate prescription of antibiotics for URTIs is still a known problem in Australia, there is a need for consistent, clear communication around antibiotics’ lack of impact on symptoms and a high association with undesirable side effects.
Does cannabis legalisation change healthcare utilisation? A population-based study using the healthcare cost and utilisation project in Colorado, USA
Authors: Delling Francesca N , Vittinghoff Eric , Dewland Thomas A , Pletcher Mark J , Olgin Jeffrey E , Nah Gregory , Aschbacher Kirstin , Fang Christina D , Lee Emily S , Fan Shannon M , Kazi Dhruv S , Marcus Gregory M
Published: May 2019

Objective

To assess the effect of cannabis legalisation on health effects and healthcare utilisation in Colorado (CO), the first state to legalise recreational cannabis, when compared with two control states, New York (NY) and Oklahoma (OK).

Design

We used the 2010 to 2014 Healthcare Cost and Utilisation Project (HCUP) inpatient databases to compare changes in rates of healthcare utilisation and diagnoses in CO versus NY and OK.

Setting

Population-based, inpatient.

Participants

HCUP state-wide data comprising over 28 million individuals and over 16 million hospitalisations across three states.

Main outcome measures

We used International Classification of Diseases-Ninth Edition codes to assess changes in healthcare utilisation specific to various medical diagnoses potentially treated by or exacerbated by cannabis. Diagnoses were classified based on weight of evidence from the National Academy of Science (NAS). Negative binomial models were used to compare rates of admissions between states.

Results

In CO compared with NY and OK, respectively, cannabis abuse hospitalisations increased (risk ratio (RR) 1.27, 95% CI 1.26 to 1.28 and RR 1.16, 95% CI 1.15 to 1.17; both p<0.0005) post-legalisation. In CO, there was a reduction in total admissions but only when compared with OK (RR 0.97, 95% CI 0.96 to 0.98, p<0.0005). Length of stay and costs did not change significantly in CO compared with NY or OK. Post-legalisation changes most consistent with NAS included an increase in motor vehicle accidents, alcohol abuse, overdose injury and a reduction in chronic pain admissions (all p<0.05 compared with each control state).

Conclusions

Recreational cannabis legalisation is associated with neutral effects on healthcare utilisation. In line with previous evidence, cannabis liberalisation is linked to an increase in motor vehicle accidents, alcohol abuse, overdose injuries and a decrease in chronic pain admissions. Such population-level effects may help guide future decisions regarding cannabis use, prescription and policy.
Environmental correlates of sedentary time and physical activity in preschool children living in a relatively rural setting in the Netherlands: a cross-sectional analysis of the GECKO Drenthe cohort
Authors: Lu Congchao , Huang Guowei , Corpeleijn Eva
Published: May 2019

Objectives

This study examined the relationship between environmental correlates and children’s sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) in preschool children.

Design

Cross-sectional study

Setting

A birth cohort in Drenthe, a northern province and relatively rural area of the Netherlands.

Participants

Valid data both for the ActiGraph and the questionnaire were obtained from 505 child–parent pairs.

Primary and secondary outcome measures

ST, LPA and MVPA of children were objectively measured by ActiGraph accelerometry (minimum three wearing days, more than 10 hours/day). Environmental correlates were collected using a questionnaire reported by parents that included household characteristics, parental and children’s PA behaviours and neighbourhood environment (eg, traffic safety, road network and presence of PA facilities). Potential correlates were identified using linear regression analysis, adjusted by age, gender, siblings, and maternal age and education level. Ordinary least square regression-based path analysis was used to estimate direct and indirect effects on activity outcomes in mediation models.

Results

Linear regression analysis showed that ‘parents taking children to play sports’ was related to less ST, more LPA and MVPA; more outdoor play was also related to less ST and more LPA, but not MVPA. Parents who perceived more PA facilities in their neighbourhood showed more support for ‘taking children to play sports’, and this was associated with less ST or more MVPA compared with children living with less PA facilities in their neighbourhood. No evidence was found for a relation between traffic safety or road network with ST, LPA and MVPA.

Conclusions

This study indicated that parental support and child outdoor play may influence children’s daily PA patterns. Convenient neighbourhood PA facilities, such as parks and playgrounds, had an indirect effect through parental support associated with lower children’s ST and higher MVPA, even in relatively rural areas.
MyBackPain—evaluation of an innovative consumer-focused website for low back pain: study protocol for a randomised controlled trial
Authors: Hall Leanne M , Ferreira Manuela , Setchell Jenny , French Simon , Kasza Jessica , Bennell Kim L , Hunter David , Vicenzino Bill , Dickson Chris , Hodges Paul
Published: May 2019

Introduction

Despite the prevalence of low back pain (LBP) worldwide, many people with the condition do not receive evidence-based care or achieve the best possible outcomes. There is a gap in the dissemination of evidence-based information across the globe. The advent of the internet has changed the way people obtain health information. As such, trustworthy, tailored and validated LBP resources may help bridge the gap. This study aims to measure the effectiveness of a new website (MyBackPain) in improving spinal health literacy, treatment preferences and clinical outcomes for people with LBP, in comparison with other online resources.

Methods and analysis

This online, pragmatic, randomised controlled trial will comprise 440 people with non-specific LBP of any duration. In addition to access to publicly available online information (control group), the intervention group will be given access to the MyBackPain.org.au website. Participants and research staff, including the biostatistician, will be blinded to treatment allocation. Data will be collected at baseline, 1, 3 (primary end-point), 6 and 12 months via online surveys and questionnaires. The primary outcome is spinal health literacy. Secondary outcomes include quality of treatment preferences (stated and observed) and LBP clinical outcomes (pain, disability and quality of life). Analyses will be by intention-to-treat and include outcome data on all randomised participants. Descriptive statistics will be presented for demographic and clinical characteristics.

Ethics and dissemination

This trial has been prospectively registered with the Australian New Zealand Clinical Trials Registry and has ethical approval from the University of Queensland Human Research Ethics Committee (2017000995). Trial outcomes will be shared via national and international conference presentations and peer-reviewed journal publications.

Trial registration number

ACTRN12617001292369; Pre-results.
Efficacy of coenzyme Q10 in patients with chronic kidney disease: protocol for a systematic review
Authors: Xu Yongxing , Liu Juan , Han Enhong , Wang Yan , Gao Jianjun
Published: May 2019

Introduction

Coenzyme Q10 (CoQ10) is a fat-soluble vitamin-like quinone that exerts antioxidative functions and is also an important factor in mitochondrial metabolism. Plasma concentrations of CoQ10 are depressed in patients with chronic kidney disease (CKD). CoQ10 supplement can reduce adverse cardiovascular events, improve mitochondrial function and decrease oxidative stress in patients with non-dialysis CKD and dialysis CKD. We performed this study as a systematic review to comprehensively assess the effect of CoQ10 supplement on patients with CKD.

Methods and analysis

The present systematic review protocol is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols guidelines. The MEDLINE, EMBASE and Cochrane library databases will be searched without language restrictions in December 2018. Two reviewers will independently screen the references in two stages: screening of the title/abstract and then of the full-text, to identify references meeting the inclusion criteria. A descriptive overview and tabular and/or graphical summaries will be generated, and directed content analysis will be carried out on the extracted data.

Ethics and dissemination

This systematic review will evaluate the efficacy and safety of CoQ10 in patients with CKD. Ethical approval is not required for this study. The results of this systematic review will be presented in relevant conferences and published in a peer-review journal.

PROSPERO registration number

CRD42019120201
Low systemic arterial compliance is associated with increased cardiovascular morbidity and mortality in aortic valve stenosis
Authors: Bahlmann Edda , Cramariuc Dana , Saeed Sahrai , Chambers John B , Nienaber Christoph A , Kuck Karl-Heinz , Lønnebakken Mai Tone , Gerdts Eva
Published: May 2019

Objective

Lower systemic arterial compliance (SAC) is associated with increased cardiovascular morbidity and mortality in hypertension, but this has not been assessed in a prospective study in aortic valve stenosis (AS).

Methods

Data from 1641 patients (38% women) with initially asymptomatic mild-moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study was used. Median follow-up was 4.3 years. SAC was assessed from Doppler stroke volume index to central pulse pressure ratio and considered low if ≤0.64 mL/m², corresponding to the lower tertile in the population. The association of SAC with outcome was assessed in Cox regression analysis and reported as HR and 95% CI.

Results

Low SAC at baseline was characterised by older age, female sex, hypertension, obesity, presence of a small aortic root, lower mean aortic gradient and more severe AS by effective aortic valve area (all p<0.01). In Cox regression analysis adjusting for factors, low SAC was associated with higher HRs for cardiovascular death (HR 2.13(95% CI 1.34 to 3.40) and all-cause mortality (HR 1.71(95% CI 1.23 to 2.38)), both p=0.001). The results did not change when systolic or diastolic blood pressure, other measures of AS severity or presence of discordantly graded AS were included in subsequent models. Presence of low SAC did not improve mortality prediction in reclassification analysis.

Conclusions

In patients with AS without diabetes and known cardiovascular disease, but a high prevalence of hypertension, low SAC was associated with higher cardiovascular and all-cause mortality independent of well-known prognosticators.

Trial registration number

NCT00092677; Post-results.
Waiting for a miracle or best medical practice? End-of-life medical ethical dilemmas in Bahrain
Authors: Alwadaei Sayed , Almoosawi Barrak , Humaidan Hani , Dovey Susan
Published: May 2019

Background and objectives

In Bahrain, maintaining life support at all costs is a cultural value considered to be embedded in the Islamic religion. We explore end-of-life decision making for brain dead patients in an Arab country where medical cultures are dominated by Western ideas and the lay culture is Eastern.

Methods

In-depth interviews were conducted from February to April 2018 with 12 Western-educated Bahraini doctors whose medical practice often included end-of-life decision making. Discussions were about who should make withdrawal of life support decisions, how decisions are made and the context for decision making. To develop results, we used the inductive method of thematic analysis.

Results

Informants considered it difficult to engage non-medical people in end-of-life decisions because of people’s reluctance to talk about death and no legal clarity about medical responsibilities. There was disagreement about doctors’ roles with some saying that end-of-life decisions were purely medical or purely religious but most maintaining that such decisions need to be collectively owned by medicine, patients, families, religious advisors and society. Informants practised in a legal vacuum that made their ethics interpretations and clinical decision making idiosyncratic regarding end-of-life care for brain dead patients. Participants referred to contrasts between their current practice and previous work in other countries, recognising the influences of religious and cultural dimensions on their practice in Bahrain.

Conclusions

End-of-life decisions challenge Western-trained doctors in Bahrain as they grapple with aligning respect for local culture with their training in the ethical practice of Western medicine.
Against the nihilism of ‘legal age change’: response to Räsänen
Authors: Saad Toni C
Published: May 2019

Räsänen has attempted to make a moral case for permitting some people to change their legal age: if someone considers that their chronological age does not correspond to their emotional age or biological age, and they face age-based discrimination as a result, they may change the legal record of their age. This response considers some of the problems with Räsänen’s paper, including its reliance on equivocation. It concludes that what is billed as a moral argument turns out to be a conflicted case for deception which relies on a nihilistic outlook on reality.
Drug-eluting stents in large coronary vessels improve both safety and efficacy compared with bare-metal stents in women: a pooled analysis of the BASKET-PROVE I and II trials
Authors: Bjerking Louise Hougesen , Hansen Kim Wadt , Sørensen Rikke , Prescott Eva , Biering-Sørensen Tor , Jeger Raban , Kaiser Christoph , Pfisterer Matthias , Galatius Søren
Published: May 2019

Background

Drug-eluting stents (DES) have proven superior to bare-metal stents (BMS) in terms of safety and efficacy. However, inference to the female subgroup has been limited by low enrolment rates of women in clinical trials. The objective of this study was to investigate the safety and efficacy of DES versus BMS in women and men.

Methods

In a pooled analysis of two all-comers randomised trials (Basel Stent Kosten-Effektivitäts Trial–Prospective Validation Examination (BASKET-PROVE) and BASKET-PROVE II) (n=4605), we examined safety and efficacy of DES versus BMS according to sex. Patients were followed 2 years for a composite endpoint of cardiac death, non-fatal myocardial infarction (MI) and clinically driven target-vessel revascularisation not related to MI.

Results

Among the 1076 women and 3529 men included in the analysis, 65.6% of the women and 67.2% of the men were randomised to receive DES. At baseline, men had more complex coronary artery disease than women. After 2 years, DES reduced rates of major adverse cardiac events (MACE) compared with BMS in both women (cumulative incidence, 6.1% vs 14.7%; adjusted HR 0.36 (95% CI 0.24 to 0.54)) and men (7.7 vs 12.1%, HR 0.62 (0.50 to 0.77)), although the reduction in MACE rates was more pronounced in women (adjusted p=0.02 for sex-stent interaction). Event rates were lower in DES for both safety and efficacy outcomes, with the largest effect seen for non-MI TVR, in both women (2.3 vs 9.2%, adjusted HR 0.24 (0.13 to 0.44)) and men (4.0 vs 7.8%, adjusted HR 0.48 (0.36 to 0.64)) (adjusted p=0.049 for sex-stent interaction).

Conclusions

In patients requiring stenting of large coronary arteries, DES were associated with improved safety in women and superior efficacy in both sexes as compared with BMS.
Variation in the position of the conus medullaris and dural sac in adult dogs
Authors: Khan Zohra , Munro Elizabeth , Shaw Darren , Faller Kiterie ME
Published: May 2019

Although it has long been stated that the level of spinal cord termination varies depending on the size of the dog, the evidence for this remains limited. The aim of this study is to investigate the position of the conus medullaris (CM) and dural sac (DS) in a population of dogs of varying size. MRIs of the thoracolumbosacral spine of 101 dogs were included. The location of CM and DS was determined on sagittal T2‐weighted images and T1‐weighted images, respectively, by three independent observers. The bodyweight and the back length were used as markers of size. Regression analysis showed that the termination point of the CM had a statistically significant relationship with bodyweight (R2=0.23, P<0.05). Although not statistically significant (P=0.058), a similar relationship was found between CM and back length (R2=0.21). No statistically significant relationship was found between the termination point of the DS and bodyweight (P=0.24) or back length (P=0.19). The study confirms the terminal position of the CM is dependent on size, with a more cranial position with increasing size; however, the termination point of DS remains constant irrespective of dog size.
Incremental sheet metal forming of Ti–6Al–4V alloy for aerospace application
Authors: Mohanraj R. , Elangovan S.
Published: May 2019

Driven by an increasing demand from the aerospace industry, thin sheet forming of titanium and its alloys is gaining prominence in scientific research. The design and manufacture of aerospace components requires the utmost precision and accuracy. It is essential to have good control over the process parameters of the forming process. Processes such as incremental sheet metal forming (ISMF) are highly controlled in the current manufacturing environment, but improvements in geometric accuracy and thinning are still needed. Although ISMF has greater process competence for manufacturing airframe structures with minimal costs, the process has its own negative effect on geometric accuracy due to elastic springback and sheet thinning. In this study, finite element analysis and experimental work are performed, considering process parameters such as spindle speed, feed rate, step depth, and tool diameter, to study the geometric accuracy and thinning of Ti–6Al–4V alloy sheet, while incrementally forming an aerospace component with asymmetrical geometry. The results are useful for understanding the geometric accuracy and thinning effects on parts manufactured by single point incremental forming (SPIF). Results from finite element analysis and experimental work are compared and found to be in good agreement.
Semantically Explainable Fuzzy Classifier
Authors: Sabol Patrik , Sinčák Peter , Magyar Jan , Hartono Pitoyo
Published: May 2019

In machine learning, there are many high-performance classifiers. However, because of lack of transparency, they are not able to explain the data in a human-friendly form. In this paper, Cumulative Fuzzy Class Membership Criterion (CFCMC), a recently proposed fuzzy modeling classifier, is modified and utilized for a novel approach of information extraction from the labeled data. This approach is able to explain the classifiability of the data in the form of semantics. Extracted semantics give information about the structure of the data and the similarities between classes. To get a relevant image of its classification performance, it is compared to three well-known and frequently used classifiers, which are considered as black boxes, namely, SVM, MLP, and kNN, and to a similar transparent approach, MF ARTMAP. To validate extracted semantics, they are compared to visualization of classified data and to confusion matrices generated during the evaluation of the created CFCMC models. The experimental result shows that CFCMC is not necessarily the best classifier, although, in most cases, it is not too far from the best performing methods. However, the semantical explanation potentially allows the classifier to be applied as a support for human decision processes in real-world problems.
Multi-Response Optimization of Machining Process Parameters for Wire Electrical Discharge Machining of Lead-Induced Ti-6Al-4V Alloy Using AHP–TOPSIS Method
Authors: Ram Prasad A. V. S. , Ramji Koona , Kolli Murahari , Vamsi Krishna G.
Published: May 2019

In this study, the effects of the process parameters on their performance characteristics of lead-induced Ti-6Al-4V alloy were investigated. Taguchi’s [Formula: see text] orthogonal array (OA) has been used to conduct the experiments. Four process parameters were considered each at three levels. Peak current, pulse-on-time, servo voltage and pulse-off-time were selected as process parameters on performance characteristics, namely, material removal rate (MRR), surface roughness (SR) and dimensional deviation (DD). A multi-attribute decision-making (MADM) technique, namely, analytic hierarchy process (AHP) and technique for order of preference by similarity to ideal solution (TOPSIS), has been used to investigate the multiple response characteristics. The weights for performance characteristics are determined by AHP. Finally, analysis of variance method has been employed effectively to bring out the influence of the process parameters associated with each performance characteristic, namely, maximization of MRR and minimization of SR and DD.
Sovereignty, Law, and Money: New Developments
Authors: Carruthers Bruce G. , Arslan Melike
Published: May 2019

Money has remained closely connected to political sovereignty even as polities changed from empires and kingdoms to dictatorships and democracies, and as money shifted from coin to paper and now to digital currency. Money constitutes a claim on value in exchange and a store and measure of value, so we consider the role law plays in these three articulations between money and value. We examine research on different instances of legal control over official currency, monetary innovations, standards of monetary measurement and valuation, counterfeiting, terror financing, and money laundering to show how the relationship between money and law has evolved in response to changes in international law, national sovereignty, and global markets.
Protein Acetylation in Bacteria
Authors: VanDrisse Chelsey M. , Escalante-Semerena Jorge C.
Published: May 2019

Acetylation is a posttranslational modification conserved in all domains of life that is carried out by N-acetyltransferases. While acetylation can occur on Nα-amino groups, this review will focus on Nε-acetylation of lysyl residues and how the posttranslational modification changes the cellular physiology of bacteria. Up until the late 1990s, acetylation was studied in eukaryotes in the context of chromatin maintenance and gene expression. At present, bacterial protein acetylation plays a prominent role in central and secondary metabolism, virulence, transcription, and translation. Given the diversity of niches in the microbial world, it is not surprising that the targets of bacterial protein acetyltransferases are very diverse, making their biochemical characterization challenging. The paradigm for acetylation in bacteria involves the acetylation of acetyl-CoA synthetase, whose activity must be tightly regulated to maintain energy charge homeostasis. While this paradigm has provided much mechanistic detail for acetylation and deacetylation, in this review we discuss advances in the field that are changing our understanding of the physiological role of protein acetylation in bacteria.
Ocular Carotenoid Status in Health and Disease
Authors: Sauer Lydia , Li Binxing , Bernstein Paul S.
Published: May 2019

Retinal carotenoids are dietary nutrients that uniquely protect the eye from light damage and various retinal pathologies. Their antioxidative properties protect the eye from many retinal diseases, such as age-related macular degeneration. As many retinal diseases are accompanied by low carotenoid levels, accurate noninvasive assessment of carotenoid status can help ophthalmologists identify the patients most likely to benefit from carotenoid supplementation. This review focuses on the different methods available to assess carotenoid status and highlights disease-related changes and potential nutritional interventions.
A combination of active learning strategies improves student academic outcomes in first-year paramedic bioscience
Authors: Sinnayah Puspha , Rathner Joseph A. , Loton Daniel , Klein Rudi , Hartley Peter
Published: May 2019

Bioscience is a foundational unit (subject) of undergraduate allied health degree programs, providing students the scientific basis underpinning their clinical practice. However, despite its significance, bioscience is a difficult academic hurdle for many students to master. The introduction of active learning strategies, including small team-based guided-inquiry learning approaches, has been shown to significantly reduce this hurdle and improve assessment outcomes for the learner. Guided team-based activities can aid in this approach by also building broader skills and capabilities, like teamwork and communication, as well as subject-specific knowledge and skills, thereby positively influencing student assessment outcomes. This paper details the redesign and evaluation of two first-year Bioscience for Paramedics units with the introduction of guided-inquiry learning, as well as other active learning strategies, and assesses their impact on student performance. Results indicate that active learning used within a classroom and in the large lecture theater setting improved students’ grades with positive student perception of their learning experience.
MiR-144 mediates Nrf2 inhibition and alveolar epithelial dysfunction in HIV-1 transgenic rats
Authors: Kukoyi Abiodun T. , Fan Xian , Staitieh Bashar S. , Hybertson Brooks M. , Gao Bifeng , McCord Joe M. , Guidot David M.
Published: May 2019

Chronic HIV infection causes redox stress and increases the risk of acute and chronic lung injury, even when individuals are adherent to antiretroviral therapy. HIV-1 transgene expression in rats inhibits nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which regulates antioxidant defenses and alveolar epithelial cell (AEC) barrier function, but the mechanism is unknown. In this study, we present novel evidence that these pathological effects of HIV are mediated by microRNA-144 (miR-144). HIV-1 transgene expression in vivo increases the expression of miR-144 in the alveolar epithelium, and this can be replicated by direct exposure of naïve primary AECs to either Tat or gp120 ex vivo. Further, treating naïve primary AECs with a miR-144 mimic decreased the expression and activity of Nrf2 and inhibited their barrier formation. In contrast, treatment with a miR-144 antagomir increased the expression and activity of Nrf2 and improved barrier function in primary AECs isolated from HIV-1 transgenic rats. Importantly, either delivering the miR-144 antagomir intratracheally, or directly activating Nrf2 by dietary treatment with PB123, increased Nrf2 expression and barrier formation in HIV-1 transgenic rat AECs. This study provides new experimental evidence that HIV-induced inhibition of Nrf2 and consequent AEC barrier dysfunction are mediated via miR-144, and that these pathophysiological effects can be mitigated in vivo by either directly antagonizing miR-144 or activating Nrf2. Our findings suggest that targeting the inhibition of Nrf2 in individuals living with HIV could enhance their lung health and decrease the lung-specific morbidity and mortality that persists despite antiretroviral therapy.