bluuebunny/crossref_metadata_2025_split huggingface dataset:
P146 Undertaking an integrated nurse led review (INCLUDE) for patients with inflammatory conditions: does it change management of morbidities?
Authors: Hider Samantha , Machin Annabelle , Bucknall Milica , Cooke Kendra , Jinks Clare , Healey Emma , Finney Andrew , Cooke Kelly , Wathall Simon , Mallen Christian , Chew-Graham Carolyn 
Published: April 2020

Abstract

Background
People with inflammatory rheumatological conditions (IRCs), including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), are at an increased risk of common comorbidities, such as cardiovascular disease (CVD), osteoporosis and mood problems, which result in poorer patient outcomes. The INCLUDE study assessed the feasibility of conducting a randomised controlled trial (RCT) of a nurse-led, holistic, integrated review in primary care.

Methods
A pilot cluster RCT was delivered across four general practices. Patients with a Read code for an IRC were recruited by postal invitation. In intervention practices (n = 2), eligible patients were invited to attend a nurse-delivered INCLUDE review - an integrated consultation assessing CVD risk (QRisk2), bone health (FRAX) and mood (PHQ2 and GAD2), using a study-specific computerised template. Patients received an individualized patient management plan, including signposting to additional services as appropriate. Medical record review was undertaken (in consenting participants) at 12 months. We compared primary care contacts (which include consultations, letters and test results) and prescribing rates (of antihypertensives, lipid-lowering, osteoporosis and antidepressant/anxiety medication) at baseline and 12 months.

Results
333 patients participated in the study. The mean (SD) age was 68.2 (13.4) years and 200 (60%) were female. Of these 172 (52%) had RA and 88 (26%) had PMR. 154 (46%) reported high blood pressure, 70 (21%) existing anxiety/depression and 37 (11%) osteoporosis. Medical record data was available for 299/333 participants. Participants in intervention practices had more primary care contacts (mean 29 vs 22). Over the 12-month follow-up, there was higher prescribing of all medication classes in participants in intervention practices (see Table), particularly so for osteoporosis medication (baseline 29% vs 12 month 46%).

Conclusion
Nurse-delivered integrated reviews for patients with IRCs identified a significant comorbidity burden. Practices undertaking these reviews had higher prescribing rates at 12 months following treatment of previously un-identified conditions, suggesting that patients with IRCs would benefit from an integrated care review to identify and manage common morbidities.

Disclosures
S. Hider None. A. Machin None. M. Bucknall None. K. Cooke None. C. Jinks None. E. Healey None. A. Finney None. K. Cooke None. S. Wathall None. C. Mallen None. C. Chew-Graham None.
P190 Non-GCA diagnoses from a GCA fast track clinic: a single centre with four years' experience (2016-2019)
Authors: kayani Abdul , Sebastian Alwin , Ranasinghe Chavini , Whitlock Madeline , Hussain Hadi , Dasgupta Bhaskar 
Published: April 2020

Abstract

Background
Giant cell arteritis (GCA) has protean manifestations including temporal headache, visual disturbances, constitutional symptoms, jaw and tongue pain; symptoms which overlap with other conditions which mimic GCA. An important benefit of a fast-track clinic (FTC) is to rapidly exclude the diagnosis GCA to avoid inappropriate steroid exposure. We analysed data for patients referred with suspected GCA to our FTC where GCA diagnosis was subsequently excluded with fast-track ultrasound (US) and other investigations.

Methods
This retrospective data was extracted from the GCA fast-track electronic referral system at Southend University Hospital from January 2016 to July 2019.

Results
1,057 patients were seen at the fast-track clinic in this study period (Table 1). 690 (65.28%) were females. Only 15% (159) of the participants had a confirmed diagnosis of GCA (majority using US but also with other investigations such as biopsy or PET CT). Non-GCA patients accounted for 85% (898) and had a variety of differential diagnoses. In 222 (23.7%) no additional diagnosis was made after excluding GCA and patients were referred back for an expectant follow-up and assessment should any new features develop. In 204 (22.7%), polymyalgia rheumatica (PMR) was diagnosed with classical clinical symptoms and US of bilateral glenohumeral joints or response to a trial of low dose oral steroids. Another major group had different types of headaches 141 (15.71%) at presentation mimicking GCA. This included migraine 79 (56.0%), cervicogenic 58 (41.13%) and cluster headaches 4 (2.83%). Infectious causes were limited to head and neck infections 89 (9.91%) such as periorbital swelling, shingles and sinusitis. Neurological causes such as cervical spondylosis, cranial nerve palsy and TIA contributed to 7.9%. Chronic pain and other causes contributed 74 (8.24%) and 97 (10.8%) respectively. Other causes included medication-related (33), stress (21), cancer (4), RS3PE (4), glaucoma (2) and ANCA-associated vasculitis (33).

Conclusion
An FTP clinic not only diagnoses GCA rapidly but is also able to rapidly screen non GCA and prevent unnecessary steroid treatment. It also requires a screening tool like GCA probability score to triage referrals to enable a more efficient service.

Disclosures
A. kayani None. A. Sebastian None. C. Ranasinghe None. M. Whitlock None. H. Hussain None. B. Dasgupta Consultancies; Roche, Sanofi, GSK. Grants/research support; Roche.
P270 Comparing the visual analogue scale (VAS) and the numerical rating scale (NRS) in patient reported outcomes in PsA
Authors: Ye Weiyu , Hackett Simon , Vandevelde Claire , Twigg Sarah , Coates Laura C 
Published: April 2020

Abstract

Background
The visual analogue scale (VAS), a 100mm horizontal line, is commonly used for many outcomes including pain in psoriatic arthritis (PsA). However, it can be susceptible to measurement error. The numerical rating scale (NRS), a 21-point scale, overcomes these limitations, however, is not yet validated in PsA. We aimed to assess the agreement and reliability of the VAS and NRS scales in PsA.

Methods
Data was collected prospectively across three UK hospital trusts from 2018-2019. All patients completed VAS and NRS for pain, arthritis, psoriasis, and global disease activity. A subset was given an identical pack to complete one week later. Mean with standard deviation (S.D.) was calculated and variability assessed using the Bland-Altman method. Intraclass correlation coefficients (ICC, two-way mixed model absolute agreement) was used to assess test-retest reliability. All analyses were performed using R. This study was approved by London-Surrey Research Ethics Committee.

Results
210 patients completed the study; one withdrew consent thus 209 were analysed. 62 patients completed the scales one week later. 60.0% were male, mean age was 51.7 years, and median PsA duration was 7.0 years. The mean (S.D.) scores are detailed in the table. For all 4 variables, the difference between the VAS and NRS scales mostly lie within 1.96 S.D. of the mean, as assessed using the Bland-Altman method, suggesting reasonable agreement between the two scales. The NRS is preferred by patients. Comparing clinic and 1-week VAS scores, the ICCs for pain, psoriasis, arthritis and global disease activity were 0.91 (95% CI 0.84-0.94), 0.93 (0.87-0.96), 0.85 (0.74-0.91), 0.89 (0.81-0.93), respectively. For NRS, the ICCs for pain, psoriasis, arthritis, and global disease activity were 0.93 (0.88-0.96), 0.89 (0.82-0.94), 0.91 (0.84-0.94), 0.91 (0.85-0.95), respectively. This suggests both scales have excellent test-retest reliability.

Conclusion
The VAS and NRS scales show reasonable agreement in patient reported pain, psoriasis, arthritis and global disease activity, and thus the NRS could be used to measure these outcomes in patients with PsA. Considering its lower likelihood of measurement error, faster speed to score, and better acceptability to patients, the NRS offers a feasible alternative to the VAS in clinical practice.

Disclosures
W. Ye None. S. Hackett None. C. Vandevelde None. S. Twigg None. L.C. Coates: None.
The COVID-19 Global Pandemic: Implications for People With Schizophrenia and Related Disorders
Authors: Kozloff Nicole , Mulsant Benoit H , Stergiopoulos Vicky , Voineskos Aristotle N 
Published: April 2020

Abstract
The coronavirus disease-19 (COVID-19) global pandemic has already had an unprecedented impact on populations around the world, and is anticipated to have a disproportionate burden on people with schizophrenia and related disorders. We discuss the implications of the COVID-19 global pandemic with respect to: (1) increased risk of infection and poor outcomes among people with schizophrenia, (2) anticipated adverse mental health consequences for people with schizophrenia, (3) considerations for mental health service delivery in inpatient and outpatient settings, and (4) potential impact on clinical research in schizophrenia. Recommendations emphasize rapid implementation of measures to both decrease the risk of COVID-19 transmission and maintain continuity of clinical care and research to preserve safety of both people with schizophrenia and the public.
Mockticals: Student‐Directed Anatomy Mock Practical Exams in a Cadaver Laboratory
Authors: Kruse Amelia , Huetteman Helen , Harvey Rachel , Gemechu Jickssa , Barremkala Malli 
Published: April 2020

The simulation testing process is helpful for students to test their knowledge of material (
Dobson, 2013), familiarize themselves with the exam format, and become acquainted with the high‐stress environment associated with test‐day. Although many schools conduct similar mock‐exams (
Nwachukwu et al, 2015;
McNulty et al, 2015), there is no literature to date standardizing how this should be performed or to provide evidence supporting the exam’s unique benefits to students who take it or organize it. This abstract demonstrates an effective model for implementation of the mocktical (mock‐practical) exam and its perceived benefits.During the foundational anatomical course for first‐year medical students at Oakland University William Beaumont School of Medicine, students demonstrate their anatomy knowledge on four exams, each including written and laboratory components. Three first‐year students, designated as pod leaders (PLs), volunteer to organize and lead a mocktical the week prior to the actual exam. PLs are responsible for organizing a third of the mocktical and can take the remaining two‐thirds without advantage, so they start by splitting the 24 dissection tables into three pods. To generate well‐rounded test questions and tags, PLs delegate two categories to each table based on class material and dissection quality. Students may submit structures and the designated PL will prepare questions, or they may submit a structure and question together. The morning of the mocktical, anatomy course directors and PLs review all tags and questions.Question categories include structures from cadavers, osteology, imaging, and histology. During the mocktical, students from each table take the exam in group format to simplify the movement of roughly 125 students through the lab. Nonetheless, each student takes the exam individually, maintaining silence, and each table will have no more than two questions. A timer is set for every 60 seconds to indicate that students should rotate, resulting in each group switching to the next table every two minutes. Total exam time is approximately 48 minutes. Upon completion, PLs display answer keys on in‐lab computers, and students are free to review and collaboratively discuss. Faculty are available for the next hour to answer questions and review topics of confusion. It should be noted that mockticals are in no way mandatory, yet we have observed nearly 99% participation, supporting the value of this process.
Cervical spinal V2a neurons pattern respiratory muscle activity and enhance ventilation
Authors: Jensen Victoria N. , Saeed Azl , Seedle Kari A. , Turner Sarah Marie , Crone Steven A. 
Published: April 2020

Our prior studies suggested that one subset of V2a neurons activates accessory respiratory muscles whereas another subset of V2a neurons actively prevents their activation at rest. However, since these studies altered V2a neuron excitability throughout the spinal cord and brainstem, it was not clear whether the V2a neurons that activate accessory respiratory muscles are located in the same region of the neuraxis as V2a neurons that prevent activation of accessory respiratory muscles at rest. Therefore, we used a Cre‐dependent AAV virus injected into a Chx10Cre/+ mouse to selectively target either the excitatory (Gq)‐ or inhibitory (Gi)‐DREADD receptor to cervical spinal V2a neurons on one side or both sides of the cord in order to alter V2a neuron excitability. Whole breath plethysmography (WBP) and electromyography (EMG) were recorded in conscious mice at rest to measure ventilation and respiratory muscle activity before and after altering V2a neuron excitability. We found that bilaterally increasing the excitability of cervical spinal V2a neurons increases accessory respiratory muscle (scalene) activity, diaphragm EMG peak amplitude, and ventilation. Although V2a neurons project ipsilaterally, increasing their excitability on one side of the cord is able to synchronously activate scalene muscles on both sides of the body. Bilaterally silencing cervical spinal V2a neurons also activates scalene muscle activity, but does not impair diaphragm function. Our results are consistent with the hypothesis that one subset of V2a neurons in the cervical spinal cord activates accessory respiratory muscles whereas another subset of cervical V2a neurons inhibits accessory respiratory muscles at rest.Support or Funding Information1RO1NS112255T32NS5007453University of Cincinnati Dean’s Dissertation Completion Fellowship
Trafficking of a Resistance to Thyroid Hormone Syndrome Mutant: A Role of Calcium Signaling?
Authors: O’Dwyer Jerry 
Published: April 2020

Thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily that serve as transcription factors for thyroid hormone‐responsive genes. TRs undergo nucleocytoplasmic shuttling mediated by nuclear localization signals (NLS) and nuclear export signals (NES) that interact with importins and exportins, respectively. Mutations in TRs offset the balance between import and export, and TR mislocalization has been hypothesized to contribute to disease pathogenesis such as in cancer and Resistance to Thyroid Hormone (RTH) syndrome
(1). Severe bone malformations and delayed linear growth often characterize the phenotype of patients with RTH syndrome. A patient with a specific, atypical RTH point mutation in TRα1 (N359Y) also exhibit hypercalcemia
(2). The purpose of this study was to quantify the intracellular localization pattern of RTH(N359Y) and to test the hypothesis that calcium plays a role in regulating trafficking of this RTH mutant.First, we performed in silico protein prediction modelling for both wild‐type TRα1 and RTH(N359Y). Both TRs have similar structure overall with perturbations in the DNA‐binding‐domain and Hinge domain. Transient transfection of HeLa (human) cells with GFP‐tagged wild‐type TRα1 and RTH(N359Y) were utilized to quantify the distribution patterns through the nuclear‐to‐cytoplasmic fluorescence ratio. RTH(N359Y) had similar localization patterns compared to wild‐type (p>0.05), with both receptors primarily localized to the nucleus. In contrast, when exposed to calcium‐enriched media, RTH(N359Y) showed a significantly increased nuclear localization compared to the wild‐type (p<0.05).To further test our hypothesis, we examined the distribution patterns of a membrane‐associated, N‐terminal truncated TRα1, namely p30, which has been reported to associate with Caveolin‐1 in the lipid‐microdomain with other proteins involved with the cGMP‐NO signaling cascade
(3). Despite lacking the DNA‐binding‐domain, p30 reconstituted in MC3T3 lead to T3‐dependent proliferation. Therefore, if p30 localizes at the plasma membrane with Caveolin‐1, thyroid hormone stimulation could mediate import of calcium from the extracellular media and serve as an in vivo approach to test the impact of calcium on receptor trafficking for wild‐type TRα1 and RTH(N359Y). Confocal analysis, however, showed that GFP‐tagged p30 does not localize at the plasma membrane, up to 36 hours post‐transfection. Therefore, other approaches will need to be utilized to ascertain the role of calcium in the trafficking of this RTH mutant.An understanding of how calcium regulates the trafficking of RTH(N359Y) could provide insight into the connection between RTH syndrome and hypercalcemia and more generally the synergistic role of calcium signaling and nuclear trafficking.Support or Funding InformationNIH Grant #2R15DK058028 to L.A.A.
Knockout of Adam10 and Tfcp2l1 in mCCDcl1 Collecting Duct Cells Demonstrates Notch‐Dependent Cell Plasticity and Phenotype
Authors: Assmus Adrienne , Mullins Linda , Peter Audrey , Mullins John 
Published: April 2020

The kidney cortical collecting duct (CCD) is responsible for the fine tuning of sodium, volume, and acid‐base homeostasis, and comprises of principal and intercalated cells (PCs and ICs) as well as a newly discovered ‘intermediate’ cell type
(1). Plasticity between PCs and ICs has been reported previously in mice in which genes for factors implicated in the Notch pathway, such as Adam10 and Tfcp2l1, have been knocked out (KO)
(2,
3). In vivo, disruption of the Notch pathway leads to a decreasing PC:IC ratio. The self‐immortalized mouse CCD cell line, mCCDcl1, shows functional characteristics of PCs and a response to physiological concentrations of hormones such as aldosterone; it also has been shown to express both PC and IC markers, a phenotype transmitted through single cell cloning
(4). These characteristics make mCCDcl1 cells a useful platform for the study of plasticity in the CCD. Tfcp2l1 and Adam10 were knocked out in mCCDcl1 cells using CRISPR‐Cas9 technology and independent clones were isolated and expanded for study. Despite mCCDcl1 cells being
polyploid, our strategy enabled all alleles for each gene to be successfully targeted and the knockout clones were verified using T7 endonuclease analysis, DNA sequencing and immunocytochemistry. Clones were cultured on Transwell filters over 10 days and their electrophysiological properties measured (trans‐epithelial resistance Rte, voltage Vte, calculated short‐circuit current Isc). Both Adam10 KO clones showed a slightly reduced baseline Rte compared to control (0.90±0.19 kΩ.cm2 vs 1.12±0.18 kΩ.cm2) but a complete reduction in baseline Isc (0.3±0.1 mA/cm2 vs −8.1±0.4 mA/cm2 for control) as well as aldosterone response, decreased by 95% (
fold change 0.19±0.03 down 3.70±0.11 for control). Both Tfcp2l1 KO clones failed to form a resistive cell monolayer, with a dramatic decrease in Rte compared to control (down to 0.10±0.02 kΩ.cm2) as well as a complete disappearance of baseline and epithelial sodium channel (ENaC) mediated amiloride‐sensitive
current. These data suggest that genomic modification of mCCDcl1 cells provides an effective means to investigate the mechanisms through which CCD cells mediate their plasticity and, in combination with single cell RNA‐Seq data, will identify new pathways involved in regulating cell phenotype.Support or Funding InformationBritish Heart Foundation Centre for Research Excellence (BHF, RE/13/3/30183) Kidney Research UK (KRUK, RP/026/20180305)
Investigation into the Role of Histone H3 Lysine 4 in Developmental Gene Regulation
Authors: Anyetei-Anum Cyril S. , McKay Daniel J. 
Published: April 2020

Histone H3 lysine 4 (H3K4) methylation is an evolutionarily‐conserved modification of chromatin closely linked to gene activation. H3K4 monomethylation (me1) is associated with active enhancers and flanks promoters. H3K4 dimethylation (me2) is enriched at tissue‐specific transcription factor binding sites, enhancers, and promoter edges. H3K4 trimethylation (me3) defines active transcriptional initiation at promoters. H3K4me1, me2, and me3 in Drosophila melanogaster is mediated by the methyltransferases Trr, dSet1, and Trx. The human homologs of these enzymes (MLL3/4, SET1A/B, and MLL1/2, respectively) perform conserved roles in human gene regulation and are commonly mutated in cancers. While these histone‐modifying enzymes have been found to be major regulators of development, differentiation, and disease, their enzymatic activity is not limited to histones and they also have non‐enzymatic functions. For these reasons, the specific role of H3K4 modification in transcriptional regulation is not understood. To directly test the function of H3K4 in animal development, we mutated H3K4 in Drosophila melanogaster. In this approach, the endogenous wild‐type histone genes are replaced with transgenic versions that have been mutated to encode a non‐modifiable residue (H3K4R). Notably, Drosophila is the only animal experimental system in which histone gene replacement can be performed because histone genes exist in high copy numbers and at multiple locations throughout the genome of most animals. By contrast, the canonical histone genes in Drosophila are clustered in a single chromosomal locus, allowing for its precise deletion
(1). Previously, we showed that wild‐type replacement transgene supports the propagation of a stable stock lacking all endogenous histone genes
(1). By contrast, here we find that H3K4R replacement transgenes result in embryonic lethality. Thus, H3K4 modification is essential for animal development. In future work, we will determine the effects of H3K4 mutation on gene expression through RNA‐seq analysis, as well as its impact on the histone post‐translational modification landscape through mass spectrometry. Together, this work will extend our understanding of the mechanistic role that histone modifications contribute to developmental gene regulation.Support or Funding InformationNIH to DJM R35‐GM128851