bluuebunny/crossref_metadata_2025_split huggingface dataset:
History Taking Skills
Authors: Mehta Gautam , Iqbal Bilal , Bowman Deborah 
Published: November 2020

Abstract
Recent years have seen a shift in the perception of communication skills from being considered subjective personal traits, to an objective, evidence-based curriculum of skills and techniques. This development was founded on the recognition that core communication skills are identifiable, can be taught, and form the basis of the majority of professional encounters. The core skills required for the patient interview in the MRCP (PACES) examination can be broadly divided into three areas: content skills, process skills, and perceptual skills. The content of the medical interview refers to the information the candidate is attempting to gather, or to give, during the course of the interview. The detail of this content is covered in the subsequent case histories of this book. However, the ability of the candidate to communicate or acquire this content depends largely on the process of the interview, and their perceptual skills. The process of the interview refers to the manner in which the candidate communicates with the patient. Although the candidate’s agenda may be to establish the content of the interview, this will not be successful unless the patient’s agenda in considered. In Stations 2 and 4 of the PACES examination, the candidate is provided with clear written instructions (such as a GP letter), followed by 14 minutes for patient interaction. The candidate then has 1 minute for reflection, followed by 5 minutes of discussion with the examiners. Despite the limited time available in the PACES Stations 2 and 4, the examiners will expect the candidate to develop rapport, show empahty, appropriately use silencce during the interview, and interpret non-verbal cues. Indeed, these processes are the key to obtaining the content of the interview, not just for the examination but also for clinical practice. Perceptual skills refer to the candidate’s decision making, problem solving, and clinical reasoning skills. These are complex, higher-order skills, which reflect the individual’s attitudes, beliefs, and self-perception. Indeed, if the content of the interview reflects the candidate’s ‘knowledge’, and the process of the interview is a reflection of ‘technique’, then these perceptual skills are a demonstration of appropriate ‘behaviour’ or ‘performance’.
Basic procedures
Authors: Chan Weng C , White Peter D 
Published: November 2020

Abstract
A number of excellent descriptions of the techniques related to peptide chain assembly have already been published. These processes are also described in the operator manuals supplied by the peptide synthesis instrument manufacturers. Accordingly, the treatment of the subject presented here has been kept brief in order to provide more space in this volume for those topics not covered in detail in other publications of this type. The protocols have been written as they would be carried out using a manual peptide synthesis vessel. Whilst it is appreciated that most scientists preparing peptides will be using automated peptide synthesizers, it is not possible, given the wide variation in operating procedures, to describe how such methods may be applied to individual instruments. Particular emphasis has been given here to those operations which are typically carried out off-instrument, such as first residue attachment and peptide-resin cleavage. The operations described in this chapter can be carried out in a purpose-built peptide synthesis vessel or in a sintered glass funnel fitted with a three-way stopcock. The operation of the system is extremely simple: solvents are added from the top of the vessel, ensuring any resin adhering to the sides is rinsed down into the resin bed; the resin bed is agitated by setting the tap to position 1 to allow flow of nitrogen to the reaction vessel; solvents and reagents are removed by setting the tap to position 2 to connect the vessel to the vacuum. The use of such vessels has previously been described in detail. Peptide synthesis resins are extremely fragile and the beads, if wrongly handled, can easily fracture, leading to the generation of fines which can block reaction vessel filter-frits and solvent lines. It is particularly important that the correct method is used for mixing the resin and soluble reactants. Polystyrene-based supports are best agitated by bubbling an inert gas through the resin bed, or by shaking or vortexing the reaction vessel. Whilst all of these approaches are employed in commercial synthesizers, gas-bubbling and shaking are the most appropriate for use in manual synthesis.
Difficult peptides
Authors: Quibell Martin , Johnson Tony 
Published: November 2020

Abstract
Solid phase peptide synthesis (SPPS), first proposed by R. B. Merrifield in 1962, has evolved over three decades into a tremendously powerful method for the preparation of peptides and small proteins. An absolute prerequisite for successful syntheses in all solid phase schemes is that reactions which accumulate solid supported products, and by the very nature of the technique contaminating by-products, must proceed cleanly and efficiently. During the earlier years of SPPS this optimal situation was not always achieved, primarily due to contaminated reagents and ill-defined polymers in combination with poorly flexible protection strategies. As the methods of SPPS gained popularity and more widespread application, reagents and protection strategies were improved and refined. However, reports of notable successful syntheses were accompanied by then unexplained failures, which have since been collectively termed ‘difficult peptides’. This chapter describes how an intrinsic understanding behind the occurrence of ‘difficult peptides’ has accumulated, leading to a general synthetic solution—the utilization of a backbone amide protection strategy. Within a few years of the introduction of SPPS, it was recognized that the assembly of some peptide sequences posed a special synthetic problem. The main feature evident during these syntheses was a sudden decrease in reaction kinetics, leading to incomplete amino-acylation by activated amino acid residues. The unreacted sites were readily detected by the Kaiser test for free amine; however, couplings showed no significant improvement even upon repeated or prolonged reaction. Efficient reactions are known to occur within a fully solvated peptide-polymer matrix, where reagent penetration is rapid and unhindered. This optimal situation no longer exists during the assembly of a difficult peptide, where the normally accessible solid phase reaction matrix becomes partially inaccessible during assembly. This situation arises suddenly, typically 6-12 residues into the synthesis, and may then persist for a number of cycles before easing, or in extreme cases remain throughout the completion of the assembly. The crude products are particularly poor if slower coupling β-branched residues (isoleucine, valine, threonine) are introduced after the onset of synthetic difficulties. The principles underlying the occurrence of difficult peptide sequences have for many years been the focus of intense debate and research. An intrinsic feature of the numerous ideas proposed is that aggregation occurs resulting in poor solvation within the peptide-polymer matrix.
Diseases of the oral mucosa
Authors: Robinson Max , Hunter Keith , Pemberton Michael , Sloan Philip 
Published: November 2020

Abstract
The oral mucosa lines the oral cavity and comprises a surface squamous epithelium with underlying lamina propria. Below the mucosa is the submucosa, which is composed of fibrous tissue and adipose tissue, and contains lobules of minor salivary glands and neurovascular bundles. In places, there is no submucosa and the lamina propria is continuous with periosteum, forming the resilient mucoperiosteum that covers the maxilla and mandible. The squamous epithelium is composed of keratinocytes arranged in lay­ers: there is a basal cell layer that rests on the basement membrane, a prickle cell layer, and usually a keratinized layer. The keratino­cytes are attached to each other by desmosomes and the basal keratino­cytes are attached to the basement membrane by hemi- desmosomes. The basement membrane is important in maintaining the integrity of the mucosa by sticking the squamous epithelium to the underlying lamina propria. There are two patterns of keratinization: par­akeratosis and orthokeratosis. In parakeratinized epithelium the surface keratinocytes become flattened and the nucleus becomes dark and shrunken (pyknotic). These terminally differentiated squamous cells are eventually lost at the surface by desquamation. In orthokeratiniza­tion, there is a granular cell layer (containing numerous keratohyaline granules) between the prickle cell layer and the keratinized layer. The surface squames become flattened and do not contain any discernible nuclear material. Whilst the majority of cells in squamous epithelium are keratinocytes, there are also accessory cells such as melanocytes, Langerhans cells, and neurosensory cells (Merkel cells and taste buds). The lamina propria is the connective tissue that lies immediately below the epithelium. It is divided into the superficial papil­lary layer (sometimes referred to as the corium) and the deeper reticu­lar layer. The lamina propria is composed of fibrous tissue with a rich neurovascular supply and contains fibroblasts that elaborate collagen and elastin fibres along with other extracellular matrix proteins. The lamina propria also contains components of the mucosal immune defence system such as Langerhans cells, macrophages, mast cells, and lymphocytes. The clinical appearance of the oral mucosa is dependent on the thick­ness of the epithelium, the amount of surface keratinization, melanin (and other) pigmentation, and the vascularity of the lamina propria.
Oral manifestations of systemic disease
Authors: Robinson Max , Hunter Keith , Pemberton Michael , Sloan Philip 
Published: November 2020

Abstract
This chapter emphasizes the importance of oral disease in the context of systemic disease. Oral disease may be the first sign of an underlying systemic disorder, which should trigger further investigations or referral to a medical or specialist practitioner, expediting early diagnosis and appropriate clinical care. In those patients with known illnesses, dental healthcare professionals should have an appreciation of the effects of these diseases on the oro- facial complex; patients can then benefit from the supportive care of the dental team. Coeliac disease (gluten-induced enteropathy) is a genetically deter­mined inflammatory small bowel disease that is induced by gluten in the diet. Gluten is present in wheat, rye, and barley. The inflammatory reaction results in malabsorption due to morphological abnormalities in the small intestinal mucosa. It was once thought of as a rare disease of childhood, but now it is understood to be a common disease that can be diagnosed at any age. Studies undertaken since the advent of sero­logical screening indicate a prevalence of 0.5–1% in the population, with adult presentations now more frequent than childhood ones. This new appreciation has led to the concept of the ‘coeliac iceberg’. At the tip of the iceberg are those with overt disease, with the lower groups classified in order as: silent coeliac disease, latent coeliac disease, and healthy individuals with genetic susceptibility. Severe presentations in childhood classically were of diarrhoea, failure to thrive, and weakness. However, it is now understood that patients with coeliac disease may have minimal gastrointestinal symptoms of malabsorption at presenta­tion and experience other rather non-specific symptoms of the disease. The increasing recognition of the disease is attributed to several factors, including new serological assays, advances in flexible endoscopy allow­ing clinicians to take duodenal biopsies more easily, and an increased index of suspicion in looking for the disease. The disease is associated with an increased rate of osteoporosis, infertility, autoimmune diseases, and malignancy, especially lymphoma. Treatment should involve a gluten-free diet, which is a major undertaking and for which dietetic advice is essential.
Image Force on a Screw Dislocation Inside an Elastic or a Piezoelectric Inhomogeneity of Arbitrary Shape
Authors: Wang Xu , Yang Ping , Schiavone Peter 
Published: November 2020

Summary
A novel and effective method is proposed to determine the image force acting on a screw dislocation located inside an elastic inhomogeneity of arbitrary shape perfectly bonded to an infinite elastic matrix. The basis for our representation of the image force stems from the fact that the analytic function defined inside the elastic inhomogeneity can be conveniently constructed from the continuity conditions of traction and displacement across the perfect interface. An identical method is employed to derive the image force on a screw dislocation inside a piezoelectric inhomogeneity of arbitrary shape.
De novo lupus nephritis during treatment with belimumab
Authors: Parodis Ioannis , Vital Edward M , Hassan Sabih-Ul , Jönsen Andreas , Bengtsson Anders A , Eriksson Per , Leonard Dag , Gunnarsson Iva , Rönnblom Lars , Sjöwall Christopher 
Published: November 2020

Abstract

Objective
In light of reports of de novo LN during belimumab (BLM) treatment, we sought to determine its frequency and contributing or protective factors in a real-life setting.

Methods
Patients with SLE who received BLM between 2011 and 2017 at five European academic practices were enrolled (n = 95) and followed longitudinally for a median time of 13.1 months [interquartile range (IQR): 6.0–34.7]; 52.6% were anti-dsDNA positive, 60.0% had low complement levels, and 69.5% had no renal involvement prior to/at BLM initiation [mean disease duration at baseline: 11.4 (9.3) years]. Age- and sex-matched patients with non-renal SLE who had similar serological profiles, but were not exposed to BLM, served as controls (median follow-up: 132.0 months; IQR: 98.3–151.2).

Results
We observed 6/66 cases (9.1%) of biopsy-proven de novo LN (4/6 proliferative) among the non-renal BLM-treated SLE cases after a follow-up of 7.4 months (IQR: 2.7–22.2). Among controls, 2/66 cases (3.0%) of de novo LN (both proliferative) were observed after 21 and 50 months. BLM treatment was associated with an increased frequency and/or shorter time to de novo LN [hazard ratio (HR): 10.7; 95% CI: 1.7, 67.9; P = 0.012], while concomitant use of antimalarial agents along with BLM showed an opposing association (HR: 0.2; 95% CI: 0.03, 0.97; P = 0.046).

Conclusion
Addition of BLM to standard-of-care did not prevent LN in patients with active non-renal SLE, but a favourable effect of concomitant use of antimalarials was implicated. Studies of whether effects of B-cell activating factor inhibition on lymphocyte subsets contribute to LN susceptibility are warranted.
Polymyositis: is there anything left? A retrospective diagnostic review from a tertiary myositis centre
Authors: Loarce-Martos Jesus , Lilleker James B , Parker Matthew , McHugh Neil , Chinoy Hector 
Published: November 2020

Abstract

Objective
The current classification criteria for idiopathic inflammatory myopathy (IIM) retain PM as a major disease subgroup. However, evolution in the understanding of IIM has suggested that many of these patients could be better described as having an alternative diagnosis. In the present study, we apply the latest understanding of IIM subtyping to retrospectively review PM diagnoses in a large cohort of IIM patients.

Methods
Within a previously reported cohort of 255 patients from a UK tertiary myositis clinic, 37 patients classified as PM according to both the EULAR/ACR IIM criteria and expert opinion were identified. Clinical data and complementary tests were reviewed, and consensus decisions regarding final classification were reached in each case.

Results
Nine (9/37, 24.3%) patients remained classified as PM, 3.5% (9/255) of the original cohort; these PM patients were seronegative for myositis antibodies, responsive to immunosuppression, and in 4/7 (57.1%) patients where muscle biopsy was performed had HLA-1 upregulation and endomysial inflammatory infiltrates. Immune-mediated necrotizing myopathy (5/37, 13.5%) and connective tissue disease overlap myositis (7/37, 19%) were the main alternative diagnoses. The remaining patients were diagnosed as: unspecified myopathy (6/37, 16%), dermatomyositis (2/37, 5%), cancer-associated myopathy (3/37, 8.1%), and non-inflammatory myopathy (1/37, 3%, myofibrillar myopathy). Four patients (4/37, 10%) had insufficient data available to confidently reclassify.

Conclusion
Our study confirms that PM can now be considered a rare IIM subgroup. A thorough examination, complete myositis autoantibody panel, and careful interpretation of the biopsy results is recommended to confirm the correct IIM sub-type.
Overcoming Rest–Task Divide—Abnormal Temporospatial Dynamics and Its Cognition in Schizophrenia
Authors: Northoff Georg , Gomez-Pilar Javier 
Published: November 2020

Abstract
Schizophrenia is a complex psychiatric disorder exhibiting alterations in spontaneous and task-related cerebral activity whose relation (termed “state dependence”) remains unclear. For unraveling their relationship, we review recent electroencephalographic (and a few functional magnetic resonance imaging) studies in schizophrenia that assess and compare both rest/prestimulus and task states, ie, rest/prestimulus–task modulation. Results report reduced neural differentiation of task-related activity from rest/prestimulus activity across different regions, neural measures, cognitive domains, and imaging modalities. Together, the findings show reduced rest/prestimulus–task modulation, which is mediated by abnormal temporospatial dynamics of the spontaneous activity. Abnormal temporospatial dynamics, in turn, may lead to abnormal prediction, ie, predictive coding, which mediates cognitive changes and psychopathological symptoms, including confusion of internally and externally oriented cognition. In conclusion, reduced rest/prestimulus–task modulation in schizophrenia provides novel insight into the neuronal mechanisms that connect task-related changes to cognitive abnormalities and psychopathological symptoms.
Impact of a 50-Year Premedical Postbaccalaureate Program in Graduating Physicians for Practice in Primary Care and Underserved Areas
Authors: Smitherman Herbert C. , Aranha Anil N.F. , Matthews De’Andrea , Dignan Andrew , Morrison Mitchell , Ayers Eric , Robinson Leah , Smitherman Lynn C. , Sprague Kevin J. , Baker Richard S. 
Published: November 2020

Purpose
To evaluate the effectiveness of Wayne State University School of Medicine’s (WSUSOM’s) 50-year premedical postbaccalaureate program (PBP)—the first and oldest in the United States—in achieving its goals, as measured by medical school matriculation and graduation, primary care specialization, and current practice location.

Method
A retrospective study of a complete comparative dataset of 9,856 WSUSOM MD graduates (1979–2017) was performed in July–August 2018. This included 539 graduates who were admitted to the PBP between 1969 and 2012. Data collected included PBP students’ sociodemographics, postgraduate specialization, residence location at time of admission to the PBP, and current medicine practice location. Health professional shortage areas (HPSAs) and medically underserved areas/populations (MUA/Ps) were determined for residence at admission to the PBP and current medicine practice location.

Results
Of the 539 PBP students, 463/539 (85.9%) successfully completed the PBP and matriculated to WSUSOM. Of those, 401/463 (86.6%) obtained an MD, and of those, 233/401 (58.1%) were female and 277/401 (69.1%) were African American. Average investment per PBP student was approximately $52,000 and for an MD graduate was approximately $77,000. The majority of PBP MD graduates with current practice information resided in HPSAs or MUA/Ps at admission to PBP (204/283, 72.1%) and were currently practicing in HPSAs or MUA/Ps (232/283, 82.0%), and 139/283 (49.1%) became primary care physicians (PCPs). Comparison of WSUSOM PBP and non-PBP MD graduates showed PBP physicians become PCPs and practice in HPSAs or MUA/Ps at higher rates than non-PBP physicians (P < .001).

Conclusions
The PBP was successful in graduating a large proportion of physicians from socioeconomically disadvantaged and diverse backgrounds, who practice as PCPs and who practice in HPSAs and MUA/Ps, thereby accomplishing the PBP’s goals of helping to address the broad health care needs of all people in the United States.
A Novel Epidemiological Approach to Geographically Mapping Population Dry Eye Disease in the United States Through Google Trends
Authors: Azzam Daniel B. , Nag Nitish , Tran Julia , Chen Lauren , Visnagra Kaajal , Marshall Kailey , Wade Matthew 
Published: November 2020

Purpose:
Our study fills the spatiotemporal gaps in dry eye disease (DED) epidemiology by using Google Trends as a novel epidemiological tool for geographically mapping DED in relation to environmental risk factors.

Methods:
We used Google Trends to extract DED-related queries estimating users' intent from 2004 to 2019 in the United States. We incorporated national climate data to generate heat maps comparing geographic, temporal, and environmental relationships of DED. Multivariable regression models were constructed to generate quadratic forecasts predicting DED and control searches.

Results:
Our results illustrated the upward trend, seasonal pattern, environmental influence, and spatial relationship of DED search volume across the US geography. Localized patches of DED interest were visualized in urban areas. There was no significant difference in DED queries across the US census regions (P = 0.3543). Regression model 1 predicted DED queries per state (R2 = 0.61), with the significant predictor being urban population [r = 0.56, adjusted (adj.) P < 0.001, n = 50]; model 2 predicted DED searches over time (R2 = 0.97), with significant predictors being control queries (r = 0.85, adj. P = 0.0169, n = 190), time (r = 0.96, adj. P < 0.001, n = 190), time2 (r = 0.97, adj. P < 0.001, n = 190), and seasonality (winter r = −0.04, adj. P = 0.0196, n = 190; spring r = 0.10, adj. P < 0.001, n = 190).

Conclusions:
Our study used Google Trends as a novel epidemiologic approach to geographically mapping the US DED. Importantly, urban population and seasonality were stronger risk factors of DED searches than temperature, humidity, sunshine, pollution, or region. Our work paves the way for future exploration of geographic information systems for locating DED and other diseases through online population metrics.