bluuebunny/crossref_metadata_2025_split huggingface dataset:
When medical trainees encountering a performance difficulty: evidence from pupillary responses
Authors: Liu Xin , Sanchez Perdomo Yerly Paola , Zheng Bin , Duan Xiaoqin , Zhang Zhongshi , Zhang Dezheng 
Published: March 2022

Abstract
Background
Medical trainees are required to learn many procedures following instructions to improve their skills. This study aims to investigate the pupillary response of trainees when they encounter moment of performance difficulty (MPD) during skill learning. Detecting the moment of performance difficulty is essential for educators to assist trainees when they need it.

Methods
Eye motions were recorded while trainees practiced the thoracostomy procedure in the simulation model. To make pupillary data comparable among trainees, we proposed the adjusted pupil size (APS) normalizing pupil dilation for each trainee in their entire procedure. APS variables including APS, maxAPS, minAPS, meanAPS, medianAPS, and max interval indices were compared between easy and difficult subtasks; the APSs were compared among the three different performance situations, the moment of normal performance (MNP), MPD, and moment of seeking help (MSH).

Results
The mixed ANOVA revealed that the adjusted pupil size variables, such as the maxAPS, the minAPS, the meanAPS, and the medianAPS, had significant differences between performance situations. Compared to MPD and MNP, pupil size was reduced during MSH. Trainees displayed a smaller accumulative frequency of APS during difficult subtask when compared to easy subtasks.

Conclusions
Results from this project suggest that pupil responses can be a good behavioral indicator. This study is a part of our research aiming to create an artificial intelligent system for medical trainees with automatic detection of their performance difficulty and delivering instructional messages using augmented reality technology.
Ethics education to support ethical competence learning in healthcare: an integrative systematic review
Authors: Andersson Henrik , Svensson Anders , Frank Catharina , Rantala Andreas , Holmberg Mats , Bremer Anders 
Published: March 2022

Abstract
Background
Ethical problems in everyday healthcare work emerge for many reasons and constitute threats to ethical values. If these threats are not managed appropriately, there is a risk that the patient may be inflicted with moral harm or injury, while healthcare professionals are at risk of feeling moral distress. Therefore, it is essential to support the learning and development of ethical competencies among healthcare professionals and students. The aim of this study was to explore the available literature regarding ethics education that promotes ethical competence learning for healthcare professionals and students undergoing training in healthcare professions.

Methods
In this integrative systematic review, literature was searched within the PubMed, CINAHL, and PsycInfo databases using the search terms ‘health personnel’, ‘students’, ‘ethics’, ‘moral’, ‘simulation’, and ‘teaching’. In total, 40 articles were selected for review. These articles included professionals from various healthcare professions and students who trained in these professions as subjects. The articles described participation in various forms of ethics education. Data were extracted and synthesised using thematic analysis.

Results
The review identified the need for support to make ethical competence learning possible, which in the long run was considered to promote the ability to manage ethical problems. Ethical competence learning was found to be helpful to healthcare professionals and students in drawing attention to ethical problems that they were not previously aware of. Dealing with ethical problems is primarily about reasoning about what is right and in the patient’s best interests, along with making decisions about what needs to be done in a specific situation.

Conclusions
The review identified different designs and course content for ethics education to support ethical competence learning. The findings could be used to develop healthcare professionals’ and students’ readiness and capabilities to recognise as well as to respond appropriately to ethically problematic work situations.
Predicting miRNA-disease associations via layer attention graph convolutional network model
Authors: Han Han , Zhu Rong , Liu Jin-Xing , Dai Ling-Yun 
Published: March 2022

Abstract
Background
MiRNA is a class of non-coding single-stranded RNA molecules with a length of approximately 22 nucleotides encoded by endogenous genes, which can regulate the expression of other genes. Therefore, it is very important to predict the associations between miRNA and disease. Predecessors developed a new prediction method of drug-disease association, and it achieved good results.

Methods
In this paper, we introduced the method of LAGCN to identify potential miRNA-disease associations. First, we integrate three associations into a heterogeneous network, such as the known miRNA-disease association, miRNA-miRNA similarities and disease-disease similarities, next we apply graph convolution network to learn the embedding of miRNA and disease. We use an attention mechanism to combine embedding from multiple convolution layers. Unobserved miRNA-disease associations are scored based on integrated embedding.

Results
After fivefold cross-validations, the value of AUC is reached 0.9091, which is higher than other prediction methods and baseline methods.

Conclusions
In this paper, we introduced the method of LAGCN to identify potential miRNA-disease associations. LAGCN has achieved good performance in predicting miRNA-disease associations, and it is superior to other association prediction methods and baseline methods.
Impact of a system to assist in clinical decision-making in primary healthcare in Catalonia: prescription Self Audit
Authors: Pons-Mesquida M. Àngels , Oms-Arias Míriam , Figueras Albert , Diogène-Fadini Eduard 
Published: March 2022

Abstract
Background
In 2008, in the context of a complete computerisation of medical records, the Institut Català de la Salut (ICS, Catalan Health Institute) implemented a system in its electronic clinical workstation (ECW) to assist decision-making at the prescription level. This system is known as Self Audit, and it supports physicians in reviewing the medication of their patients. Self Audit provides lists of patients presenting medication-related problems (MRPs) that have potential for improvement, and provides therapeutic recommendations that are easy to apply from the system itself. The aim of this study was to analyse the main results derived from the use of Self Audit in primary care (PC) in Catalonia, and the effect of an incentive-based safety indicator on the results obtained.

Methods
A descriptive cross-sectional study was carried out to analyse variations in the MRPs detected by Self Audit during 2016, 2017, and 2018 in PC in Catalonia. The effect of a safety indicator on the results obtained was also studied. This safety indicator includes the most clinically relevant MRPs (i.e., therapeutic duplications, safety alerts from the Spanish Medicines Agency, and incidences of polymedication in patients over 65 years of age). Variation in the MRPs was measured using the differences between two evaluation points (initial and final). An MRP was considered resolved if the recommendation specified in the alert was followed. The prescriptions of 6411 PC doctors of the ICS who use the ECW and provide their services to 5.8 million Catalans through 288 PC teams were analysed.

Results
Analysis of the total safety-based MRPs detected by Self Audit gave overall resolutions from April to December of 9% (21,547) in 2016, 7% (15,924) in 2017, and 1% (2392) in 2018 out of the total number of MRPs recorded in April each year. Examination of the 3 types of MRPs with the highest clinical relevance that were linked to the safety indicator gave overall resolutions of 41% in 2016 (17,358), 20% in 2017 (7655), and 21% in 2018 (8135).

Conclusions
The ICS Self Audit tool assists in reducing the number of safety-based MRPs in a systematic manner, and yields superior results for the MRPs linked to a safety indicator included in the incentives of PC physicians.
Barriers to tuberculosis case finding in primary and secondary health facilities in Ghana: perceptions, experiences and practices of healthcare workers
Authors: Der Joyce B. , Grant Alison D. , Grint Daniel , Narh Clement T. , Bonsu Frank , Bond Virginia 
Published: March 2022

Abstract
Background
Ghana’s national tuberculosis (TB) prevalence survey conducted in 2013 showed higher than expected TB prevalence indicating that many people with TB were not being identified and treated. Responding to this, we assessed barriers to TB case finding from the perspective, experiences and practices of healthcare workers (HCWs) in rural and urban health facilities in the Volta region, Ghana.

Methods
We conducted structured clinic observations and in-depth interviews with 12 HCWs (including five trained in TB case detection) in four rural health facilities and a municipal hospital. Interview transcripts and clinic observation data were manually organised, triangulated and analysed into health system-related and HCW-related barriers.

Results
The key health system barriers identified included lack of TB diagnostic laboratories in rural health facilities and no standard referral system to the municipal hospital for further assessment and TB testing. In addition, missed opportunities for early diagnosis of TB were driven by suboptimal screening practices of HCWs whose application of the national standard operating procedures (SOP) for TB case detection was inconsistent. Further, infection prevention and control measures in health facilities were not implemented as recommended by the SOP. HCW-related barriers were mainly lack of training on case detection guidelines, fear of infection (exacerbated by lack of appropriate personal protective equipment [PPE]) and lack of motivation among HCWs for TB work. Solutions to these barriers suggested by HCWs included provision of at least one diagnostic facility in each sub-municipality, provision of transport subsidies to enable patients’ travel for testing, training of newly-recruited staff on case detection guidelines, and provision of appropriate PPE.

Conclusion
TB case finding was undermined by few diagnostic facilities; inconsistent referral mechanisms; poor implementation, training and quality control of a screening tool and guidelines; and HCWs fearing infection and not being motivated. We recommend training for and quality monitoring of TB diagnosis and treatment with a focus on patient-centred care, an effective sputum transport system, provision of the TB symptom screening tool and consistent referral pathways from peripheral health facilities.
The clinically led worforcE and activity redesign (CLEAR) programme: a novel data-driven healthcare improvement methodology
Authors: Corner Evelyn J. , Camilleri Matthew , Dholakia Shruti , Gredal Charlotte , Hansen Tina , Jeans John , LeNovere Marie , Mallender Jacqueline , Monkhouse Alex , Purkiss Claire , Ting Tai Ken , Vindrola-Padros Cecilia , Welfare Stephen , Wood Danny , Wood James ,   on behalf of the CLEAR Faculty
Published: March 2022

Abstract
Background
The NHS is facing substantial pressures to recover from the COVID-19 pandemic. Optimising workforce modelling is a fundamental component of the recovery plan. The Clinically Lead workforcE and Activity Redesign (CLEAR) programme is a unique methodology that trains clinicians to redesign services, building intrinsic capacity and capability, optimising patient care and minimising the need for costly external consultancy. This paper describes the CLEAR methodology and the evaluation of previous CLEAR projects, including the return on investment.

Methods
CLEAR is a work-based learning programme that combines qualitative techniques with data analytics to build innovations and new models of care. It has four unique stages: (1) Clinical engagement- used to gather rich insights from stakeholders and clinicians. (2) Data interrogation- utilising clinical and workforce data for cohort analysis. (3) Innovation- using structured innovation methods to develop new models of care. (4) Recommendations- report writing, impact assessment and presentation of key findings to executive boards. A mixed-methods formative evaluation was carried out on completed projects, which included semi-structured interviews and surveys with CLEAR associates and stakeholders, and a health economic logic model that was developed to link the inputs, processes, outputs and the outcome of CLEAR as well as the potential impacts of the changes identified from the projects.

Results
CLEAR provides a more cost-effective delivery of complex change programmes than the alternatives – resulting in a cost saving of £1.90 for every £1 spent independent of implementation success. Results suggest that CLEAR recommendations are more likely to be implemented compared to other complex healthcare interventions because of the levels of clinical engagement and have a potential return on investment of up to £14 over 5 years for every £1 invested. CLEAR appears to have a positive impact on staff retention and wellbeing, the cost of a CLEAR project is covered if one medical consultant remains in post for a year.

Conclusions
The unique CLEAR methodology is a clinically effective and cost-effective complex healthcare innovation that optimises workforce and activity design, as well as improving staff retention. Embedding CLEAR methodology in the NHS could have substantial impact on patient care, staff well-being and service provision.
Toxoplasma gondii is not an important contributor to poor reproductive performance of primiparous ewes from southern Australia: a prospective cohort study
Authors: Clune Thomas , Lockwood Amy , Hancock Serina , Thompson Andrew N. , Bruce Mieghan , Beetson Sue , Campbell Angus J. , Glanville Elsa , Brookes Daniel , Trengove Colin , O’Handley Ryan , Jacobson Caroline 
Published: March 2022

Abstract
Background
Toxoplasma gondii causes reproductive losses in sheep worldwide, including Australia. The reproductive performance of primiparous ewes is typically lower than for mature, multiparous ewes, and younger ewes are more likely to be immunologically naïve and therefore more susceptible to reproductive disease if T. gondii infection occurs during pregnancy. The aim of this study was to assess the impact of infection with T. gondii on the reproductive performance of primiparous ewes in southern Australia using a prospective cohort study. This will inform the need for targeted control strategies for T. gondii in Australian sheep.

Results
Toxoplasma gondii seropositivity using indirect ELISA was detected at 16/28 farms located across southern Australia. Apparent seropositivity to T. gondii was lower in primiparous ewes (1.1, 95% confidence interval (CI) 0.6, 1.8) compared to mature, multiparous ewes (8.1, 95% CI 6.0, 10.5; P < 0.001). Toxoplasma gondii seroconversion during the gestation and lambing period was confirmed for 11/1097 (1.0, 95% CI 0.5, 1.7) of pregnant primiparous ewes that failed to raise a lamb, and 1/161 (0.6, 95% CI 0.1, 2.9) primiparous ewes with confirmed mid-pregnancy abortion.

Conclusions
Low frequency of detection of T. gondii seroconversion during gestation and low frequency of seropositivity to T. gondii suggests that toxoplasmosis was not an important contributor to reproductive losses in primiparous ewes on farms located over a wide geographical area in southern Australia.
Clinical and diagnostic characteristics of complex III mitopathy due to novel BCS1L gene mutation in a Saudi patient
Authors: Al Qurashi Mansour , Mustafa Ahmed , Aga Syed Sameer , Ahmad Abrar , El-Farra Abdellatif , Shawli Aiman , Al Hindi Mohammed , Hasosah Mohammed 
Published: March 2022

Abstract
Background
Of the many types of mitochondrial diseases, mutations affecting BCS1L gene are regarded as chief cause of the defective mitochondrial complex-III, affecting normal mitochondrial functioning, and leading to wide variety of phenotypes.

Case presentation
In this case report we describe a novel genotype linked to a unique phenotype in a Saudi patient born of a consanguineous marriage. Detailed genetic analysis and whole genome sequencing identified a novel homozygous missense mutation in exon 5 c.712A > G (p.Ser328Gly) of the BCS1L gene, with predicted deleterious effects on the functioning AAA+-ATPase domain of the protein characterized by distinct clinical presentation associated with profound multisystem involvement, conductive hearing loss, absent external auditory canal, low posterior hair line, short neck, micro and retrognathia, over riding fingers, rocker bottom foot, small phallus with bilateral absent testis (empty scrotum) and intolerable lactic acidosis.

Conclusions
A pathogenic effect of this novel BCS1L mutation was reflected in the patient with his failure to thrive and a complex clinical and metabolic phenotype.
Epidemiology, healthcare utilization, and related costs among patients with IPF: results from a German claims database analysis
Authors: Kreuter Michael , Picker Nils , Schwarzkopf Larissa , Baumann Severin , Cerani Agustin , Postema Roelien , Maywald Ulf , Dittmar Axel , Langley Jonathan , Patel Haridarshan 
Published: March 2022

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a progressive form of fibrosing interstitial pneumonia with poor survival. This study provides insight into the epidemiology, cost, and disease course of IPF in Germany.

Methods
A cohort of incident patients with IPF (n = 1737) was identified from German claims data (2014–2019). Incidence and prevalence rates were calculated and adjusted for age differences compared with the overall German population. All-cause and IPF-related healthcare resource utilization as well as associated costs were evaluated per observed person-year (PY) following the initial IPF diagnosis. Finally, Kaplan–Meier analyses were performed to assess time from initial diagnosis to disease deterioration (using three proxy measures: non-elective hospitalization, IPF-related hospitalization, long-term oxygen therapy [LTOT]); antifibrotic therapy initiation; and all-cause death.

Results
The cumulative incidence of IPF was estimated at 10.7 per 100,000 individuals in 2016, 10.9 in 2017, 10.5 in 2018, and 9.6 in 2019. The point prevalence rates per 100,000 individuals for the respective years were 21.7, 23.5, 24.1, and 24.1. On average, ≥ 14 physician visits and nearly two hospitalizations per PY were observed after the initial IPF diagnosis. Of total all-cause direct costs (€15,721/PY), 55.7% (€8754/PY) were due to hospitalizations and 29.1% (€4572/PY) were due to medication. Medication accounted for 49.4% (€1470/PY) and hospitalizations for 34.8% (€1034/PY) of total IPF-related direct costs (€2973/PY). Within 2 years of the initial IPF diagnosis (23.6 months), 25% of patients died. Within 5 years of diagnosis, 53.1% of patients had initiated LTOT; only 11.6% were treated with antifibrotic agents. The median time from the initial diagnosis to the first non-elective hospitalization was 5.5 months.

Conclusion
The incidence and prevalence of IPF in Germany are at the higher end of the range reported in the literature. The main driver for all-cause cost was hospitalization. IPF-related costs were mainly driven by medication, with antifibrotic agents accounting for around one-third of the total medication costs even if not frequently prescribed. Most patients with IPF do not receive pharmacological treatment, highlighting the existing unmet medical need for effective and well-tolerated therapies.
Study on the mechanism of efficient extracellular expression of toxic streptomyces phospholipase D in Brevibacillus choshinensis under Mg2+ stress
Authors: Chen Shaofeng , Xiong Weide , Zhao Xurui , Luo Weiyi , Yan Xuhui , Lu Yinghua , Chen Cuixue , Ling Xueping 
Published: March 2022

Abstract
Background
Phospholipase D (PLD) has significant advantages in the food and medicine industries due to its unique transphosphatidylation. However, the high heterologous expression of PLD is limited by its cytotoxicity. The present study sought to develop an efficient and extracellular expression system of PLD in the non-pathogenic Brevibacillus choshinensis (B. choshinensis).

Results
The extracellular PLD was effectively expressed by the strong promoter (P2) under Mg2+ stress, with the highest activity of 10 U/mL. The inductively coupled plasma–mass spectrometry (ICP-MS) results elucidated that the over-expression of PLD by P2 promoter without Mg2+ stress induced the ionic homeostasis perturbation caused by the highly enhanced Ca2+ influx, leading to cell injury or death. Under Mg2+ stress, Ca2+ influx was significantly inhibited, and the strengths of P2 promoter and HWP gene expression were weakened. The study results revealed that the mechanism of Mg2+ induced cell growth protection and PLD expression might be related to the lowered strength of PLD expression by P2 promoter repression to meet with the secretion efficiency of B. choshinensis, and the redistribution of intracellular ions accompanied by decreased Ca2+ influx.

Conclusions
The PLD production was highly improved under Mg2+ stress. By ICP-MS and qPCR analysis combined with other results, the mechanism of the efficient extracellular PLD expression under Mg2+ stress was demonstrated. The relatively low-speed PLD expression during cell growth alleviated cell growth inhibition and profoundly improved PLD production. These results provided a potential approach for the large-scale production of extracellular PLD and novel insights into PLD function.