bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward an understanding of tissue factor pathway inhibitor‐2 as a novel serodiagnostic marker for clear cell carcinoma of the ovary
Authors: Kobayashi Hiroshi , Imanaka Shogo
Published: June 2021

Aims

Tissue factor pathway inhibitor (TFPI)‐2 has recently emerged as a serodiagnostic marker for patients with epithelial ovarian cancer (EOC), especially clear cell carcinoma (CCC). This review discusses the biological properties of TFPI‐2 and why serum levels are elevated in CCC patients.

Methods

A comprehensive literature search was conducted in PubMed up until March, 2021.

Results

TFPI‐2 is a Kunitz‐type protease inhibitor and negatively regulates the enzymatic activities, such as plasmin. TFPI‐2 has been characterized as a tumor suppressor gene and was frequently downregulated through promoter hypermethylation in various human cancers. In contrast, TFPI‐2 was overexpressed only in CCC. TFPI‐2 may be involved in the pathophysiology of CCC, possibly through regulation of coagulation system, stabilization of extracellular matrix (ECM), and induction of intracellular signal transduction. TFPI‐2 suppresses tissue factor‐induced hypercoagulation in a hypoxic environment. TFPI‐2, secreted by CCC cells, platelets, and adjacent vascular endothelial cells, may suppress tumor growth and invasion through ECM remodeling. Nuclear TFPI‐2 may suppress matrix metalloproteinase production via transcription factors and modulate caspase‐mediated cell apoptosis. CCC cells may upregulate the TFPI‐2 expression to adapt to survival in the demanding environment. TFPI‐2 is secreted by CCC cells and enters the systemic circulation, resulting in elevated blood levels.

Discussion

Serum TFPI‐2 reflects the overexpression of TFPI‐2 in CCC tissues and is a potential serodiagnostic marker. Further research is needed to explore the expression, clinical significance, biological function, and potential mechanism of TFPI‐2 in CCC.
Oral behaviours and wake‐time masseter activity in patients with masticatory muscle pain
Authors: Ramanan D. , Palla S. , Bennani H. , Polonowita A. , Farella M.
Published: June 2021

Background

Little is known about wake‐time masseter activity of patients with masticatory muscle pain in real‐life settings.

Objectives

The aims of this study were (1) to assess wake‐time masseter activity of women with masticatory muscle pain (MMP) and compare it with that of pain‐free women; and (2) to investigate the association between objectively measured masseter contractions and self‐reported oral behaviours.

Methods

Adult women (N = 27) diagnosed with MMP were age‐matched with pain‐free women (N = 26). The electromyographic (EMG) activity of the masseter muscle when awake was recorded unilaterally for two consecutive days. The number of contraction episodes and relative contraction time (%) were calculated using cut‐off thresholds of 3%, 5% and 10% of maximum voluntary contraction (MVC). Self‐reported daytime oral activity was assessed using the Oral Behaviours Checklist (OBC, items 3–21). Data were analysed using univariate tests and mixed‐model analyses.

Results

The number of contraction episodes was similar between groups for all detection thresholds, but the relative contraction time at the lower detection thresholds (i.e. 3% MVC and 5% MVC) was significantly longer (1.5‐fold) in the MMP than in the pain‐free group. The OBC scores were significantly higher in the women with MMP than in controls, but no positive association could be found between EMG variables and OBC scores.

Conclusion

Women with MMP engage in low‐level masseter muscle contractions, which last longer than those of pain‐free controls. There was no relationship between self‐reported oral behaviours and masseter activity when awake. These findings support the notion that prolonged low‐level clenching when awake may play a role in the pathophysiology of MMP.
Prevalence of allergic rhinitis with lower airways inflammation: A new endotype with high risk of asthma development?
Authors: Di Cara Giuseppe , Bizzarri Ilaria , Fabiano Cecilia , Faina Fabrizio , Di Cicco Maria , Rinaldi Victoria E , Verrotti Alberto , Peroni Diego
Published: June 2021

Aim

Asthma and allergic rhinitis share common pathophysiological mechanisms. However, while asthma phenotypes and endotypes are defined basing on both clinical and immunological features, rhinitis classification is still based on severity and frequency of symptoms. Recently, fractional exhaled nitric oxide (FeNO) has been suggested as a possible biomarker of rhinitis to asthma development. The aim of our study was to define the prevalence of a high FeNO allergic rhinitis endotype in a paediatric population of children with allergic rhinitis in order to quantify the impact of such patients in general practice.

Methods

A total of 159 children (aged 7–16 years) with allergic rhinitis and no asthmatic symptoms were enrolled in our study. Severity assessment of rhinitis and asthma was evaluated in accordance with ARIA and GINA guidelines. All patients performed the following assessments: skin prick test (SPT), spirometry and FeNO measurement.

Results

FeNO was increased in 54 (33.9%) of 159 patients. No significant correlation with age, severity and frequency of rhinitis was evidenced. Positive SPT for house dust mites was related with a higher prevalence of high FeNO (P = 0.04), with no significant correlation with other sensitisations. All patients showed normal spirometric values.

Conclusion

A possible new endotype of allergic rhinitis and lower airways inflammation showed to be significantly present in our population. The lack of correlation with allergic rhinitis severity assessment suggests that FeNO could be considered as an independent variable, possibly linked to a higher risk of asthma development in children with no lower airways symptoms and normal spirometry.
Prionosciadium guzmanianum (Apiaceae, Apioideae), a new species with red flowers from western Mexico
Authors: Cuevas‐Guzmán Ramón , del Castillo‐Batista Ana Patricia , Morales‐Arias José Guadalupe
Published: June 2021

Prionosciadium guzmanianum, a second species of Prionosciadium with red flowers is described and illustrated. The genus is almost endemic to the Mexican Republic and presents a high richness and endemism in western Mexico. Given the color of its flowers, the closest relationship of the new species is with P. tamayoi, from which it differs by the basal, ternate‐pinnatifid leaves, pinnatifid leaflets and larger orbicular fruits with central dorsal rib wing. Pollen grains are described and illustrated, and information on the habitat of the species is provided.
Carbon concentration in the world's trees across climatic gradients
Authors: Paroshy Nicholas J. , Doraisami Mahendra , Kish Rosalyn , Martin Adam R.
Published: June 2021

Wood carbon (C) concentration is a key wood trait that varies widely among tree species, but our understanding of the factors governing this trait is limited, despite reason to hypothesize that wood C varies systematically across environmental gradients.

We compiled a novel database of 1145 geo‐referenced wood C observations from 415 species, to elucidate climate correlates of wood C concentrations, and test if these relationships differ across tissue types and major taxonomic divisions (i.e. angiosperms vs gymnosperms).

Climate variables, including mean annual temperature (MAT) and precipitation and temperature seasonality, are significantly correlated with wood C concentrations. Relationships between wood C and these variables differ across tissue types and taxonomic divisions, yet there is a negative relationship between wood C and MAT that exists across all tissues and species groups.

Wood C concentrations in trees are influenced by climate, with experimental evidence (albeit scant) indicating that climate‐driven changes in lignin concentrations likely govern these relationships. Our study presents among the first lines of evidence indicating that wood C concentrations are correlated with environmental conditions, thereby enhancing our understanding of the potential adaptive significance of wood C variation in trees.
Delivery mode and the incidence of atopic sensitization and food allergy in a Finnish child population
Authors: Pyrhönen Kaisa , Kulmala Petri
Published: June 2021

Background

Caesarean section (CS) has been associated with an increased risk of subsequent atopic diseases, particularly asthma and respiratory allergies, but controversial findings have also been reported. Our aim was to clarify the association between the delivery mode and longitudinal (atopic) outcomes.

Methods

The target population was identified from the population register and comprised all children born between 2001 and 2006 and living in the province of South Karelia, Finland (N = 5564). The information on the delivery mode was available for 5552 children from the Finnish Medical Birth Register. Results of allergy tests (skin prick tests, specific IgE and open food challenges, OFCs) were collected from patient records of all healthcare units in the area.

Results

By 12 years of age, the cumulative incidence of atopic sensitization was 15% for those born by normal vaginal delivery (VD), 20% (adjusted RR 1.28; 95% CI 0.99–1.65) by assisted VD, 20% (adjusted RR 1.28; 95% CI 1.02–1.61) by elective CS and 20% (adjusted RR 1.24; 95% CI 0.99–1.56) by others, for example emergency CS. Among the offspring of mothers without atopic diseases, the incidence of food allergy (positive OFC) was 6% for those born by elective CS and 2% for those born by normal VD (adjusted RR 2.41; 95% CI 1.19–4.88), while the respective incidences were 5% and 6% (adjusted RR 0.82; 95% CI 0.33–2.06) among the offspring of mothers with atopic diseases.

Conclusion

By adolescence, the cumulative incidences of atopic sensitization was highest among those born by assisted VD or CS. The incidence of food allergy was highest among those born by elective CS among the offspring of mothers without atopic diseases.
Fibrous papules on the lips
Authors: Shi Xiuyan , Zhang Bin , Ma Lin
Published: June 2021

Multiple angiofibromas are commonly found in patients with tuberous sclerosis complex. We report a rare presentation of multiple congenital fibrous papules occurring only on the lips with no syndromic associations.
Why the Wrongness of Killing Innocent, Non‐threatening People is a Universal Moral Certainty
Authors: Laves Samuel
Published: June 2021

In a recent article in this journal, José María Ariso makes the argument that the killing of innocent, non‐threatening people is not a universal moral certainty. To make this case, he gives two examples where the certainty is seemingly not present: the pisa‐suave child soldiers in the Colombian civil war and the often‐discussed case of Nazi Germany. This paper is an attempt to respond to these criticisms. I will respond to each charge in turn and argue that they do not pose a problem to the idea that the wrongness of killing innocent, non‐threatening people is a universal moral certainty.
Sphere Of Influences In Public Policy Domain During EmergencyTo Combat COVID-19
Authors: Mohamed Yusof Nor	Ashikin , Mohamed Zamri , Saimy Intan Sazrina , Salleh Siti Hasliah
Published: June 2021

The spreading of Covid19 as a global pandemic has tested countries around the world at many levels. From mental strength to economic resiliency and far stretching to include legality of issues. A year later, the world is still not in a better place. Malaysia, like others are fighting the thirds waves of the pandemic, believed to be more fatal than before. From March 2020 until to date, Malaysians have been placed under complete lockdown before that order was relaxed and tighten again when the numbers of infected patients and deaths skyrocketed. Now Malaysia is placed under emergency order and law. Strangely the emergency order is issued while the complete and conditional Movement Control Orders (MCO) are still in effect. Since an emergency is a situation where the country could not be managed under regular administrative system, it is important to know which parties that are majorly involved in currently running the country to fight Covid19 has the overriding power over the others, what are their rights or limitations. Between the emergency order, complete MCO and conditional MCO, which one should be prioritized and how long would Malaysia remain under emergency? The answer could be found by studying the sphere of influences in the public policy domain. The article is qualitative in nature; data is collected from legal documents, judicial precedents and article writings. The sphere of influences during emergency time is more complex than usual. The legislative and executive powers are concentrated to one or two party(s) with enormous authorities and expansive jurisdictions.
Material Design for Teaching Citations Skills in Scientific Writing
Authors: Mansourizadeh Kobra , Ahmad Ummul K.
Published: June 2021

Citations are important rhetorical devices that when properly and strategically employed, allow writers to promote their current research findings persuasively and efficiently. As knowledge construction is progressive and cumulative, specifically in scientific disciplines, it is evident that acquiring skills for adequate and effective application of citations is essential for success. Scientific writers are required to possess advanced academic literacy skills in order to ably position their study within the framework of existing knowledge, and strategically employ citations to advance the acceptability of their research findings. This paper endeavors to propose materials for teaching the rhetorical functions of citations in advanced academic writing courses. The tasks are designed specifically to raise students’ awareness of citation norms, especially in their own specific disciplines. Since the practice of citing the work of others ethically is highly challenging for emerging research writers, materials suggested in this paper can be beneficial to instructors who are involved in developing advanced discipline-specific writing courses, or short-term academic writing workshops.
Effect of Stretching Rate on Tensile Response and Crystallization Behavior of Crosslinked Natural Rubber
Authors: Masa Abdulhakim , Hayeemasae Nabil , Soontaranon Siriwat , Mohd Pisal Mohd Hanif , Mohamad Rasidi Mohamad Syahmie
Published: June 2021

The performance of natural rubber (NR) relies heavily on the microstructural changes during deformation. This has brought to significant change in the stress response of NR. Besides, the stretching rate may also affect the stress response of NR. In this study, effects of stretching rate on tensile deformation and strain-induced crystallization of crosslinked NR were investigated. Results indicated that increasing the strain rate has increased the stress at given strain where the onset of strain-induced crystallization was shifted to a lower strain. The crystallinity of the crosslinked NR was shown to be higher at a high stretching rate and it corresponded well with the tensile response. The results clearly confirm that chain orientation and crystallization became stronger with increasing deformation rate. The study also suggests that the deformation could improve distribution of crosslinked network structures.
Nuclear Regulatory Acceptance of Certified Process Data Reconciliation
Authors: Jansky Andy , Langenstein Magnus
Published: June 2021

The utility industry is currently undergoing a substantial change from analogue to digital infrastructure. Not only plant performance and utility profits are dependent on accurate plant operational parameters but, more importantly, set safety limits need to be met in order to ensure safe operation of nuclear power plants in particular. Using nonquality-assured process data for operational decisions can result in significant over- or under-power events in the plant. In addition, all new technologies such as AI, IIoT, and digital twin technology rely on robust process data as input, putting at risk the significance of the results from the continuing data processing (“garbage in, garbage out”). One method, certified process data reconciliation, or certified process data reconciliation (CPDR), cuts through the vast amount of available process data and generates all relevant process values with the smallest uncertainty possible. In addition, 95% of all collected process data can be discarded after introduction of CPDR. With CPDR, plant operation and maintenance can be significantly optimized and utilities can profit by realizing, e.g., power recovery and measurement uncertainty recapture (MUR). Because the focus on reconciled instead of measured values constitutes a paradigm shift, the application of CPDR needs to be communicated to nuclear regulators. This paper describes the approach and experience of the regulator acceptance process in various countries around the globe.
Influence of Anisotropic Thermal Conductivity on Overall Cooling Effectiveness on a Film-Cooled Leading Edge
Authors: Bryant Carol E. , Rutledge James L.
Published: June 2021

Increasing interest in the use of ceramic matrix composites (CMCs) for gas turbine engine hot gas path components requires a thorough examination of the thermal behavior one may expect of such components. Their highly anisotropic thermal conductivity is a substantial departure from traditional metallic components and can influence the temperature distribution in surprising ways. With the ultimate surface temperature dependent on the internal cooling scheme, including cooling from within the film cooling holes themselves, as well as the external film cooling, the relative influence of these contributions to cooling can be affected by the directionality of the thermal conductivity. Conjugate heat transfer computational simulations were performed to evaluate the effect of anisotropy in the leading edge region of a turbine component. The leading edge region is modeled as a fully film-cooled half cylinder with a flat afterbody. Changing the anisotropic directionality of the thermal conductivity is shown to have nearly the same effect on temperature distribution over the surface of the leading edge as increasing the thermal conductivity by a factor of four. While structural considerations with CMC components are often paramount, designers should be aware of the thermal ramifications associated with the selection of the CMC lay-up.
Transporting Carrier With Droplets Driven by Electrowetting-on-Dielectric Effect
Authors: He Jian-Zhang (Kenny) , Chang Jen-Yuan (James)
Published: June 2021

In the early 19th century, Thomas Young (1805) and Pierre Simon Laplace (1806) published the concept of fluid surface tension, which made great contributions to the theory of surface tension. Many scholars continued to study electrowetting-on-dielectric (EWOD) technology, hoping to effectively control the movement of droplets, to make a lot of microchannels in biomedical and life applications. The purpose of dielectric and hydrophobic layer is to prevent the droplet from short circuiting when the electrode moves, and the increase of hydrophobic layer will improve the smoothness of droplet movement. EWOD technology is used in this research as the prelude of the development of soft robot. Through the combination of finger electrode and electrowetting-on-dielectric technology, a carrier is designed. The drop is driven by Arduino and LabVIEW control software, and the carrier can be moved effectively. The effective distance between the finger electrodes was found out from the experiment to change the contact angle of the drop. Drop material will use two kinds of materials, PC and mixed liquid (PC, UV), try to change the contact angle and its strength through the voltage of 0–250V, so as to find out the maximum force and suitable contact angle, hoping to support the carrier effectively. Finally, the carrier will be transported to the designated position by using drops.
Zinc and copper, by high sensitivity-low energy ion scattering
Authors: Avval Tahereh G. , Průša Stanislav , Chapman Sean C. , Linford Matthew R. , Šikola Tomáš , Brongersma Hidde H.
Published: June 2021

Low energy ion scattering (LEIS) is an extremely surface sensitive technique that can quantitatively analyze the outermost atomic layer of a material. In LEIS and high sensitivity-low energy ion scattering (HS-LEIS), straightforward quantitation is available using reference and/or standard materials. Here, we present the HS-LEIS spectra of zinc obtained with 3 keV 4He+ and 4 keV 20Ne+ projectile ions. Zinc is an important material with a wide range of applications. Thus, these spectra should be useful standards/references for future applications. A high purity zinc foil was used for these measurements after the removal of the oxide layer. As a reference for the instrumental sensitivity, the spectra for Cu from a high purity foil are also included with this submission. Atomic sensitivity and relative sensitivity factors for Zn and Cu are reported.
Correlates Between Physical Activity and Sunburn Prevalence Among a Nationally Representative Sample of US High School Students, 2015–2017
Authors: Wei Grace , Farooq Jeffrey , Castelo-soccio Leslie , Mhaskar Rahul
Published: June 2021

Background: Physical activity is associated with greater odds of sunburn in adults, increasing harmful sun exposure and skin cancer risk. The authors sought to investigate parallel associations between sunburn and physical activity among US high school students. Methods: The authors examined pooled cross-sectional data from the 2015 and 2017 Youth Risk Behavior Survey. A nationally representative sample of 21,894 US high school students who responded to the sunburn question was included. Results: Prevalence of sunburn was 56.6% between 2015 and 2017. Sunburn prevalence was higher in physically active students (88.3%; 95% confidence interval [CI], 86.7%–90.0%; P < .0001) and student athletes (63.0%; 95% CI, 59.4%–66.7%; P < .0001). Among male students who were vigorously physically active (≥5 d) or on ≥3 teams, the odds of sunburn were 2.33 (95% CI, 1.81–3.00; P < .0001) and 2.52 (95% CI, 1.96–3.23; P < .0001), respectively. Among female students who were vigorously physically active (≥5 d) or on ≥3 teams, the odds of sunburn were 1.65 (95% CI, 1.36–2.02; P < .0001) and 2.92 (95% CI, 2.07–4.13; P < .0001), respectively. Conclusions: Many US high school students are affected by sunburn, and the odds of sunburn are elevated during physical activity and team sports participation. Efforts are needed to improve sun safety regulations, education, and resources for youth during school and physical activity.
Multicomponent Gold-Linked Glycoconjugate Vaccine Elicits Antigen-Specific Humoral and Mixed T
H
1-T
H
17 Immunity, Correlated with Increased Protection against Burkholderia pseudomallei
Authors: Tapia Daniel , Sanchez-Villamil Javier I. , Stevenson Heather L. , Torres Alfredo G.
Published: June 2021

Melioidosis is a complex human disease associated with a wide range of complications caused by the Gram-negative bacillus
Burkholderia pseudomallei
. The global burden of melioidosis is estimated to have 165,000 cases per year and 89,000 fatal outcomes.
Ecogenomics of Groundwater Phages Suggests Niche Differentiation Linked to Specific Environmental Tolerance
Authors: Kothari Ankita , Roux Simon , Zhang Hanqiao , Prieto Anatori , Soneja Drishti , Chandonia John-Marc , Spencer Sarah , Wu Xiaoqin , Altenburg Sara , Fields Matthew W. , Deutschbauer Adam M. , Arkin Adam P. , Alm Eric J. , Chakraborty Romy , Mukhopadhyay Aindrila
Published: June 2021

To our knowledge, this is the first study to identify the bacteriophage distribution in a groundwater ecosystem shedding light on their prevalence and distribution across metal-contaminated and background sites. Our study is uniquely based on selective sequencing of solely the extrachromosomal elements of a microbiome followed by analysis for viral signatures, thus establishing a more focused approach for phage identifications.
Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada
Authors: Oakley Laura L , Regan Annette K , Fell Deshayne B , Spruin Sarah , Bakken Inger Johanne , Kwong Jeffrey C , Pereira Gavin , Nassar Natasha , Aaberg Kari M , Wilcox Allen J , Håberg Siri E
Published: June 2021

Objective

To assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood.

Design

Analysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates.

Setting

Population-based.

Participants

1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario).

Exposure

Clinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy.

Main outcome measures

We extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes ‘epilepsy’ and ‘febrile seizures’.

Results

Among 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester.

Conclusions

In this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures.
Dutch multidisciplinary guideline on Achilles tendinopathy
Authors: de Vos Robert-Jan , van der Vlist Arco C , Zwerver Johannes , Meuffels Duncan Edward , Smithuis Frank , van Ingen Ronald , van der Giesen Florus , Visser Edwin , Balemans Astrid , Pols Margreet , Veen Natasja , den Ouden Mirre , Weir Adam
Published: June 2021

Objective

To provide a comprehensive, evidence-based overview of the risk factors, prevention, diagnosis, imaging, treatment and prognosis for Achilles tendinopathy. To make clinical recommendations for healthcare practitioners and patients.

Design

Comprehensive multidisciplinary guideline process funded by the Quality Foundation of the Dutch Federation of Medical Specialists. This process included a development, commentary and authorisation phase. Patients participated in every phase.

Data sources

Multiple databases and existing guidelines were searched up to May 2019. Information from patients, healthcare providers and other stakeholders were obtained using a digital questionnaire, focus group interview and invitational conference.

Study eligibility criteria

Studies on both insertional and/or midportion Achilles tendinopathy were eligible. Specific eligibility criteria were described per module.

Data extraction and synthesis

To appraise the certainty of evidence, reviewers extracted data, assessed risk of bias and used the Grading of Recommendations Assessment, Development and Evaluation method, where applicable. Important considerations were: patient values and preferences, costs, acceptability of other stakeholders and feasibility of implementation. Recommendations were made based on the results of the evidence from the literature and the considerations.

Primary outcome measure

The primary and secondary outcome measures were defined per module and defined based on the input of patients obtained in collaboration with the Netherlands Patient Federation and healthcare providers from different professions.

Results

Six specific modules were completed: risk factors and primary prevention, diagnosis, imaging, treatment prognosis and secondary prevention for Achilles tendinopathy.

Summary/conclusion

Our Dutch multidisciplinary guideline on Achilles tendinopathy provides six modules developed according to the standards of the Dutch Federation of Medical Specialists. Evidence-based recommendations for clinical practice are given for risk factors, prevention, diagnosis, imaging, treatment and prognosis. This guideline can assist healthcare providers and patients in clinical practice.
Randomised controlled trial to establish the clinical and cost-effectiveness of expectant management versus preoperative imaging with magnetic resonance cholangiopancreatography in patients with symptomatic gallbladder disease undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones (The Sunflower Study): a study protocol
Authors: Clout Madeleine , Blazeby Jane , Rogers Chris , Reeves Barnaby , Lazaroo Michelle , Avery Kerry , Blencowe Natalie S , Vohra Ravi , Jennings Neil , Hollingworth William , Thorn Joanna , Jepson Marcus , Collingwood Jane , Guthrie Ashley , Booth Elizabeth , Pathak Samir , Beckingham Ian , Culliford Lucy , Griffiths Ewen A , Albazaz Raneem , Toogood Giles
Published: June 2021

Introduction

Surgery to remove the gallbladder (laparoscopic cholecystectomy (LC)) is the standard treatment for symptomatic gallbladder disease. One potential complication of gallbladder disease is that gallstones can pass into the common bile duct (CBD) where they may remain dormant, pass spontaneously into the bowel or cause problems such as obstructive jaundice or pancreatitis. Patients requiring LC are assessed preoperatively for their risk of CBD stones using liver function tests and imaging. If the risk is high, guidelines recommend further investigation and treatment. Further investigation of patients at low or moderate risk of CBD stones is not standardised, and the practice of imaging the CBD using magnetic resonance cholangiopancreatography (MRCP) in these patients varies across the UK. The consequences of these decisions may lead to overtreatment or undertreatment of patients.

Methods and analysis

We are conducting a UK multicentre, pragmatic, open, randomised controlled trial with internal pilot phase to compare the effectiveness and cost-effectiveness of preoperative imaging with MRCP versus expectant management (ie, no preoperative imaging) in adult patients with symptomatic gallbladder disease undergoing urgent or elective LC who are at low or moderate risk of CBD stones. We aim to recruit 13 680 patients over 48 months. The primary outcome is any hospital admission within 18 months of randomisation for a complication of gallstones. This includes complications of endoscopic retrograde cholangiopancreatography for the treatment of gallstones and complications of LC. This will be determined using routine data sources, for example, National Health Service Digital Hospital Episode Statistics for participants in England. Secondary outcomes include cost-effectiveness and patient-reported quality of life, with participants followed up for a median of 18 months.

Ethics and dissemination

This study received approval from Yorkshire & The Humber – South Yorkshire Research Ethics Committee. Results will be submitted for publication in a peer-reviewed journal.

Trial registration number

ISRCTN10378861.
Effect of an online healthy lifestyle psychoeducation programme to improve cardiometabolic outcomes and affective symptoms in youth receiving mental health care: study protocol for a pilot clinical trial.
Authors: Wilson Chloe , Nichles Alissa , Zmicerevska Natalia , Carpenter Joanne Sarah , Song Yun Ju Christine , McHugh Catherine , Hamilton Blake , Hockey Samuel , Scott Elizabeth M , Hickie Ian B
Published: June 2021

Introduction

Worsened cardiometabolic profiles in youth with mental ill health have been associated with a number of modifiable lifestyle risk factors. It is becoming increasingly evident that clinical interventions need to be multimodal in focus to improve mental health symptoms and the physical health symptoms in this already at-risk cohort.

Methods and analysis

This 12-week pilot clinical trial examines the efficacy, feasibility and acceptability of an adjunctive online psychoeducation programme for improving cardiometabolic risk parameters and affective symptoms in a transdiagnostic sample of at least 44 young people aged 16–25 years presenting for mental healthcare for mood and/or psychotic syndromes (including anxiety, depression, bipolar disorder and psychosis). Individuals will be invited to participate in a pilot clinical trial for a structured online psychoeducation programme incorporating nutritional, physical activity, sleep–wake and healthy lifestyle information, delivered fortnightly over six online modules. Participants will undergo a series of assessments including: (1) self-report and clinician administered assessments determining mental health symptomatology; (2) fasting blood tests to assess cardiometabolic markers (fasting insulin, fasting glucose and blood lipids); (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) sleep–wake behaviours and circadian rhythm assessments. Changes in scores for all cardiometabolic and affective measures will be assessed via paired samples t-tests, and correlations between change scores will be assessed via Pearson’s or Spearman’s correlations. Feasibility will be assessed via completion rates, and the acceptability of the programme will be assessed via programme satisfaction measures.

Ethics and dissemination

This pilot clinical trial has been approved by the Sydney Local Health District Research Ethics and Governance Office (X20-0228 & 2020/ETH01201). The results of this pilot clinical trial will be disseminated into the scientific and broader community through peer-reviewed journals, conference presentations, social media and university websites.

Trial registration number

Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12620000772943, Date 28 August 2020.
Efficacy and safety of nintedanib in Japanese patients with early-stage idiopathic pulmonary fibrosis: a study protocol for an observational study
Authors: Sakamoto Noriho , Hamada Naoki , Okamoto Masaki , Tobino Kazunori , Ichiyasu Hidenori , Ishii Hiroshi , Ichikado Kazuya , Morimoto Shimpei , Hosogaya Naoki , Mukae Hiroshi
Published: June 2021

Introduction

Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown aetiology with a poor prognosis. Several clinical trials of nintedanib in patients with IPF have reported its inhibitory effect on reduced lung function, incidence of acute exacerbation of IPF and worsened health-related quality of life. Although nintedanib has a manageable safety and tolerability profile over long-term use, it was discontinued in over 20% of patients because of adverse events such as diarrhoea and liver dysfunction. This might explain why nintedanib use in patients with IPF is not widespread, especially among patients with early-stage IPF. In the present study, we aimed to clarify the efficacy, safety and tolerability of nintedanib in patients with stage I/II IPF, based on the Japanese IPF disease severity staging classification system.

Methods and analysis

This is an ongoing, prospective, multicentre observational cohort study of patients with stage I/II IPF who will start receiving nintedanib. Totally, 215 patients at 35 sites in Kyushu and Okinawa, Japan will be enrolled and followed up for 3 years. Nintedanib therapy would be initiated at the discretion of the investigator. The primary endpoint, change in forced vital capacity (FVC) at 156 weeks, will be shown as the mean change in FVC from baseline to week 156 with 95% CIs estimated using the Wald method. The safety endpoint—occurrence of adverse events—will be assessed in each system organ class/preferred term.

Ethics and dissemination

The study protocol and informed consent documents were approved by the Institutional Review Board at Nagasaki University Hospital (approval number 19102146) and each participating site. Written informed consent was obtained from all participants. Patient recruitment has begun. The results will be disseminated through scientific peer-reviewed publications and national and international conferences.

Trial registration number

UMIN000038192.
Immersive technology in ophthalmology education: a systematic review
Authors: Lowe Shakeel , Mares Kathryn , Khadjesari Zarnie
Published: June 2021

Background

Despite the increasing use of immersive technology (IT) in ophthalmology, the effectiveness of this approach compared to other teaching practices is unclear. This systematic review aimed to determine the value of IT to teach students ophthalmic skills and whether it can supplement or replace conventional teaching practices.

Methods

A systematic search was performed of CENTRAL, MEDLINE, EMBASE, ERIC and PsychINFO databases. Randomised controlled trials comparing IT interventions versus (1) no training, (2) standard training, (3) different types of IT interventions, (4) different doses of IT interventions were eligible for inclusion.

Results

Seven trials involving 177 participants were included. IT offered some benefit compared to standard training as most trials demonstrated evidence of learning represented by composite performance score and performance time. Repetitive training with IT displayed similar results.

Conclusion

IT appears to improve the ophthalmic skill of healthcare trainees and should be considered as a supplement to training.
Heterogeneity of reasons for attendance in frequent attenders of emergency departments and its relationship to future attendance
Authors: Hotham Richard , O'Keeffe Colin , Stone Tony , Mason Suzanne M , Burton Christopher
Published: June 2021

Background

EDs globally are under increasing pressure through rising demand. Frequent attenders are known to have complex health needs and use a disproportionate amount of resources. We hypothesised that heterogeneity of patients’ reason for attendance would be associated with multimorbidity and increasing age, and predict future attendance.

Method

We analysed an anonymised dataset of all ED visits over the course of 2014 in Yorkshire, UK. We identified 15 986 patients who had five or more ED encounters at any ED in the calendar year. Presenting complaint was categorised into one of 14 categories based on the Emergency Care Data Set (ECDS). We calculated measures of heterogeneity (count of ECDs categories and entropy of categories) and examined their relationship to total number of ED visits and to patient characteristics. We examined the predictive value of these and other features on future attendance.

Results

Most frequent attenders had more than one presenting complaint type. Heterogeneity increased with number of attendances, but heterogeneity adjusted for number of attendances did not vary substantially with age or sex. Heterogeneity was associated with the presence of one or more contacts for a mental health problem. For a given number of attendances, prior mental health contact but not heterogeneity was associated with further attendance.

Conclusions

Heterogeneity of presenting complaint can be quantified and analysed for ED use: it is increased where there is a history of mental disorder but not with age. This suggests it reflects more than the number of medical conditions.
Airborne infection risk during open-air cardiopulmonary resuscitation
Authors: Dbouk Talib , Aranda-García Silvia , Barcala-Furelos Roberto , Rodríguez-Núñez Antonio , Drikakis Dimitris
Published: June 2021

Aim

Cardiopulmonary resuscitation (CPR) is an emergency procedure where interpersonal distance cannot be maintained. There are and will always be outbreaks of infection from airborne diseases. Our objective was to assess the potential risk of airborne virus transmission during CPR in open-air conditions.

Methods

We performed advanced high-fidelity three-dimensional modelling and simulations to predict airborne transmission during out-of-hospital hands-only CPR. The computational model considers complex fluid dynamics and heat transfer phenomena such as aerosol evaporation, breakup, coalescence, turbulence, and local interactions between the aerosol and the surrounding fluid. Furthermore, we incorporated the effects of the wind speed/direction, the air temperature and relative humidity on the transport of contaminated saliva particles emitted from a victim during a resuscitation process based on an Airborne Infection Risk (AIR) Index.

Results

The results reveal low-risk conditions that include wind direction and high relative humidity and temperature. High-risk situations include wind directed to the rescuer, low humidity and temperature. Combinations of other conditions have an intermediate AIR Index and risk for the rescue team.

Conclusions

The fluid dynamics, simulation-based AIR Index provides a classification of the risk of contagion by victim’s aerosol in the case of hands-only CPR considering environmental factors such as wind speed and direction, relative humidity and temperature. Therefore, we recommend that rescuers perform a quick assessment of their airborne infectious risk before starting CPR in the open air and positioning themselves to avoid wind directed to their faces.
Natriuretic peptide level at heart failure diagnosis and risk of hospitalisation and death in England 2004–2018
Authors: Taylor Clare J , Lay-Flurrie Sarah L , Ordóñez-Mena José M , Goyder Clare R , Jones Nicholas R , Roalfe Andrea K , Hobbs FD Richard
Published: June 2021

Objective

Heart failure (HF) is a malignant condition requiring urgent treatment. Guidelines recommend natriuretic peptide (NP) testing in primary care to prioritise referral for specialist diagnostic assessment. We aimed to assess association of baseline NP with hospitalisation and mortality in people with newly diagnosed HF.

Methods

Population-based cohort study of 40 007 patients in the Clinical Practice Research Datalink in England with a new HF diagnosis (48% men, mean age 78.5 years). We used linked primary and secondary care data between 1 January 2004 and 31 December 2018 to report one-year hospitalisation and 1-year, 5-year and 10-year mortality by NP level.

Results

22 085 (55%) participants were hospitalised in the year following diagnosis. Adjusted odds of HF-related hospitalisation in those with a high NP (NT-proBNP >2000 pg/mL) were twofold greater (OR 2.26 95% CI 1.98 to 2.59) than a moderate NP (NT-proBNP 400–2000 pg/mL). All-cause mortality rates in the high NP group were 27%, 62% and 82% at 1, 5 and 10 years, compared with 19%, 50% and 77%, respectively, in the moderate NP group and, in a competing risks model, risk of HF-related death was 50% higher at each timepoint. Median time between NP test and HF diagnosis was 101 days (IQR 19–581).

Conclusions

High baseline NP is associated with increased HF-related hospitalisation and poor survival. While healthcare systems remain under pressure from the impact of COVID-19, research to test novel strategies to prevent hospitalisation and improve outcomes—such as a mandatory two-week HF diagnosis pathway—is urgently needed.
Multiple sclerosis: structural and functional integrity of the visual system following alemtuzumab therapy
Authors: Wang Chenyu , Barton Joshua , Kyle Kain , Ly Linda , Barnett Yael , Hartung Hans-Peter , Reddel Stephen W , Beadnall Heidi , Taha Marinda , Klistorner Alexander , Barnett Michael Harry
Published: June 2021

Objective

To investigate potential neuroprotective and pro-remyelinating effects of alemtuzumab in multiple sclerosis (MS), using the visual pathway as a model.

Methods

We monitored clinical, multifocal visual evoked potential (mfVEP) and MRI outcomes in 30 patients commencing alemtuzumab for relapsing MS, and a reference group of 20 healthy controls (HCs), over 24 months. Change in mfVEP latency was the primary endpoint; change in optic radiation (OR) lesion diffusion metrics and Mars letter contrast sensitivity over the course of the study were secondary endpoints.

Results

In patients, we observed a mean shortening of mfVEP latency of 1.21 ms over the course of the study (95% CI 0.21 to 2.21, p=0.013), not altered by correction for age, gender, disease duration or change in OR T2 lesion volume. Mean mfVEP latency in the HC group increased over the course of the study by 0.72 ms (not significant). Analysis of chronic OR T2 lesions (patients) showed an increase in normalised fractional anisotropy and axial diffusivity between baseline and 24 months (both p<0.01). Mean Mars letter contrast sensitivity was improved at 24 months vs baseline (p<0.001), and driven by an early improvement, in both patients and HC.

Conclusion

We found evidence of partial lesion remyelination after alemtuzumab therapy, indicating either natural restoration in the context of a ‘permissive’ local milieu; or potentially an independent, pro-reparative mechanism of action. The visual system presents a unique opportunity to study function-structure specific effects of therapy and inform the design of future phase 2 MS remyelination trials.
GFAP as a biomarker in frontotemporal dementia and primary psychiatric disorders: diagnostic and prognostic performance
Authors: Katisko Kasper , Cajanus Antti , Huber Nadine , Jääskeläinen Olli , Kokkola Tarja , Kärkkäinen Virve , Rostalski Hannah , Hartikainen Paivi , Koivisto Anne M , Hannonen Sanna , Lehtola Juha-Matti , Korhonen Ville E , Helisalmi Seppo , Koivumaa-Honkanen Heli , Herukka Sanna-Kaisa , Remes Anne M , Solje Eino , Haapasalo Annakaisa
Published: June 2021

Background

Frontotemporal lobar degeneration (FTLD) and primary psychiatric disorders (PPD) are characterised by overlapping clinical features but different aetiologies. Here, we assessed for the first time the potential of blood glial fibrillar acidic protein (GFAP), marker of astrogliosis, as a discriminative and prognostic tool in FTLD and PPD.

Methods

The levels of GFAP in serum (sGFAP) of patients with FTLD (N=107) and PPD (N=44) and GFAP in whole blood samples (bGFAP) from FTLD (N=10), PPD (N=10) and healthy controls (N=18) were measured. We evaluated whether the sGFAP levels associate with C9orf72 repeat expansion, survival of FTLD and PPD patients, and brain atrophy assessed cross-sectionally and longitudinally by structural T1W MRI. We also examined the correlation between sGFAP and bGFAP levels in a subset of patients.

Results

sGFAP and bGFAP levels were elevated in the FTLD group compared with the PPD or control groups. Receiver operating characteristic analysis indicated an excellent diagnostic performance between FTLD and PPD (the area under the curve (AUC)=0.820, 95% CI 0.745 to 0.896). sGFAP and bGFAP levels showed a strong correlation and elevated sGFAP levels significantly associated with atrophy rate in the temporal cortex and predicted shorter survival time in patients with FTLD. No association with C9orf72 repeat expansion was detected.

Conclusions

sGFAP enabled differentiation of patients with FTLD and PPD and associated with shorter survival and more severe brain atrophy rate in patients with FTLD. These results suggest that blood-based GFAP represents a minimally invasive and useful biomarker in the differential diagnostics between patients with FTLD and PPD and in evaluating disease progression and astrogliosis in FTLD.