bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical assessment of salivary glands function
Authors: Tappuni Anwar R.
Published: May 2021

One of the main features of Sjögren’s syndrome (SS) is the lymphocytic infiltration of the exocrine glands, mainly of the salivary and lacrimal glands, causing gland destruction. The severity of the salivary gland dysfunction is frequently associated with disease progression. Therefore, accurate assessment of salivary flow rates has diagnostic and prognostic value. However, in addition to the serological markers, the confirmative diagnostic test for SS at present is the assessment of lymphocytic infiltrate in a minor salivary gland biopsy. As the latter is an invasive and expensive procedure, there have been studies recently advocating the benefits of salivary gland ultrasound and other noninvasive tests in diagnosing SS and in eliminating or reducing the need for a biopsy.
Imaging in Sjögren’s syndrome
Authors: Adams Ashok
Published: May 2021

Imaging has an important role in the investigation of patients with sicca symptoms. There are a number of imaging modalities and techniques available in order to aid diagnosis of Sjögren’s syndrome (SS) and attempt to differentiate from other potential causes. Imaging techniques form part of the various diagnostic criteria proposed for the diagnosis of both primary and secondary SS. The aim of this chapter is to highlight the benefits and limitations of the various imaging techniques and provide a spectrum of the imaging findings encountered in clinical practice. The chapter will also identify potential areas for future development that may assist with diagnosis and treatment of patients with SS.
Ocular manifestations of Sjögren’s syndrome
Authors: Kelly Nicola , Aragona Pasquale , Rolando Maurizio , Figueiredo Francisco C
Published: May 2021

Dry eye is among the most commonly described problems in patients with Sjögren’s syndrome (SS). This chapter describes the ocular manifestations of SS and how they are assessed in a clinical and research setting. Commonly used diagnostic tools in clinic are designed to assess both symptoms and signs of dry eye. The differences between patients’ symptoms and the objective signs that can be seen could be the result of our lack of understanding of the full disease process, as pain pathways could play an important role. However, with improvements in measurements of symptoms or different objective measurements, a better clinical picture could be provided to bridge the gap between signs and symptoms. New and less frequently used technologies such as analysis of tear proteins in search for biomarkers, conjunctival cytology, and in vivo confocal microscopy might provide promising diagnostic information for treating dry eye in patients with SS.
Renal involvement in primary Sjögren’s syndrome
Authors: Evans Rhys D. R. , Walsh Stephen B.
Published: May 2021

Renal involvement in primary Sjögren’s syndrome (pSS) was first described in the 1960s, with reports of acquired defects in tubular function, in the setting of lymphocytic tubulointerstitial inflammation. Renal involvement in pSS is common, but is frequently undiagnosed due to its covert nature. It may manifest either as epithelial disease causing tubulointerstitial nephritis, or as an immune-complex glomerulopathy. Tubulointerstitial inflammation leads to acquired defects in tubular function, which may occur at multiple nephron segments. Treatment protocols lack evidence from randomized trials, and involve immunosuppression targeting B- and T-cells, which mediate both interstitial and glomerular disease to varying extents. In this chapter, we review the prevalence of renal involvement in pSS and its clinical manifestations, likely pathogenesis, and treatment.
Gastrointestinal disease in Sjögren’s syndrome
Authors: Price Elizabeth J.
Published: May 2021

Gastrointestinal (GI) involvement is common in patients with Sjögren’s syndrome (SS): At least one-third will have GI symptoms at some point in the course of their condition, but in the majority of cases, it is mild. This chapter discusses conditions such as dysphagia and oesophageal dysfunction, gastritis, irritable bowel syndrome, coeliac disease, pancreatitis and pancreatic insufficiency, autonomic nervous system dysfunction, and liver disease. Mild elevation of liver enzymes are seen in a high proportion of patients with SS, but most of these patients are asymptomatic, and more serious disease is rare. Although rare, chronic viral hepatitis may be the cause of abnormal liver function in certain populations. Hepatitis B has been more common in Asian patients with SS, and hepatitis C is seen in Mediterranean populations. Primary biliary cholangitis is the commonest associated autoimmune liver disease. The chapter discusses the potential effects of SS on the GI system and liver.
Neurological complications of Sjögren’s syndrome
Authors: Ganesh Aravind , Lyons Shane , Yiin Gabriel
Published: May 2021

Neurological involvement is an important manifestation of Sjögren’s syndrome. The disease can affect both the central nervous system (CNS) and the peripheral nervous system (PNS), but estimates of prevalence are complicated by heterogeneity in both the definition of the symptoms or syndromes considered and the paucity of high-quality prospective data. PNS presentations include diffuse sensorimotor neuropathy, small fibre neuropathy, autonomic neuropathy, mononeuritis multiplex, dorsal root ganglionitis, and trigeminal neuropathy or neuralgia. CNS presentations are similarly protean and include diffuse or focal presentations with neuropsychiatric and cognitive symptoms, as well as myelopathy and nonspecific white matter changes. The co-occurrence of Sjögren’s syndrome with neuromyelitis optica spectrum disorders and multiple sclerosis–like presentations is an ongoing area of investigation. Where relevant, management strategies for PNS and CNS manifestations are briefly reviewed.
Cardiovascular and lung manifestations of Sjögren’s syndrome
Authors: Carty Sara
Published: May 2021

In contrast to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), where cardiovascular problems are frequent, extra-articular disease manifestations of cardiovascular disease are not commonly reported in patients with Sjögren’s syndrome (SS), and SS disease-activity measures do not feature cardiovascular disease. The prevalence appears to be higher than in the general population but lower than in RA and SLE populations, possibly due to the lower prevalence of smoking among the SS population. In contrast, respiratory disease is a well-recognized complication of SS. In this chapter cardiovascular and lung manifestations of SS mechanisms are discussed, together with therapies, as well as long-term complications including lymphoma and amyloidosis.
Sjögren’s syndrome—summary of clinical management
Authors: Price Elizabeth J. , Baer Alan N.
Published: May 2021

Managing patients with Sjögren’s syndrome (SS) in a clinical setting remains challenging despite a number of published practical management guidelines based on systematic reviews and involving both experts and patients. In this chapter we aim to provide a pragmatic guide to managing SS patients in clinic, drawing on evidence presented in this book, published guidelines, and the authors personal experience. Successful management of SS requires the physician to personalize care to the individual patient. Although dryness (sicca) of the eyes and mouth are the classically described features of SS, other mucosal surfaces may be affected, and patients may have systemic manifestations, including fatigue and arthralgia. Physicians should educate and support patients to manage their condition with interventions to conserve, replace, and stimulate secretions; prevent damage; and suppress any systemic disease activity.
Oxford Handbook of Respiratory Medicine
Authors: Chapman Stephen J , Robinson Grace V , Shrimanker Rahul , Turnbull Chris D , Wrightson John M
Published: May 2021

Revised and updated for its third edition, the Oxford Handbook of Respiratory Medicine is concise, practical, and designed for rapid access to essential information. It covers the latest clinical guidelines and developments in the field and features unique sections on practical procedures, as well as a symptoms section to aid in differential diagnosis and clinical management. Practical advice on management is integrated throughout and a dedicated section on respiratory emergencies ensures the ability to cope with any eventuality. New sections include thoracic ultrasound, indwelling pleural catheters, safe sedation, and cardiopulmonary exercise testing, and this new edition covers all major respiratory diseases and symptoms.
Diffuse lung disease
Authors: Robinson Chapman
Published: May 2021

This chapter describes a diagnostic approach, based on clinical features, imaging, and other investigations; more detailed descriptions of the diseases themselves are presented later in the book. The term ‘diffuse lung disease’ is used here to describe any widespread pulmonary disease process. Patients typically present with breathlessness and bilateral CXR shadowing. However, the rate of onset and severity of breathlessness are extremely variable, and presentations range from an asymptomatic patient with long-standing radiological changes to an acute onset of breathlessness over a period of days, leading rapidly to respiratory failure and death.
Sleep and breathing
Authors: Robinson Chapman
Published: May 2021

Sleep apnoea and related problems are now a common reason for referral to many respiratory units. This is due to much better recognition of the syndromes and the increasing prevalence of obesity. Respiratory units with sleep services are seeing increasing numbers of patients, primarily for possible OSA, and, therefore, most patients tend to be sleepy, and referrals for insomnia are not usually encouraged.
Bronchiolitis
Authors: Robinson Chapman
Published: May 2021

Bronchioles are small airways of <2 mm diameter, lined by bronchial epithelium and with no cartilage in their walls. Terminal bronchioles lead to alveoli. Many bronchioles need to be affected by disease before a patient becomes symptomatic, when there will be increased airway resistance unresponsive to β‎2 stimulants. Bronchiolitis is poorly understood and is a mixture of conditions.
Chronic obstructive pulmonary disease (COPD)
Authors: Robinson Chapman
Published: May 2021

COPD is common and is mostly caused by smoking. Patients with COPD represent a large proportion of inpatient and outpatient work for the chest physician. COPD encompasses a number of underlying pathologies, including chronic bronchitis and emphysema.
Connective tissue disease and the lung
Authors: Robinson Chapman
Published: May 2021

Patients with connective tissue diseases often develop pulmonary complications, for which they should be referred to a chest physician. Patients typically present with symptoms of dyspnoea, cough, fever, or chest pain. They may often already be on immunosuppressive drugs.
Cor pulmonale
Authors: Robinson Chapman
Published: May 2021

Cor pulmonale is the traditional term for changes in the cardiovascular system resulting from the chronic hypoxia (and usually hypercapnia) of chronic lung disease leading to pulmonary hypertension (PHT). PHT is precapillary due to raised pulmonary vascular resistance, is usually mild-moderate and does not tend to progress; a subgroup of patients may develop severe PHT, disproportionate to their lung disease. These changes present with peripheral oedema.
Cystic fibrosis (CF)
Authors: Robinson Chapman
Published: May 2021

Cystic fibrosis (CF) is a multi-system disease due to mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a complex chloride channel. CFTR is essential for regulating chloride permeability across epithelial tissues and, in addition, has other complex cellular roles. Loss of CFTR function or quantity causes inadequate hydration of mucous secretions. In the lungs this results in defective mucociliary clearance, mucus obstruction of the luminal space, and colonization with pathogenic bacteria. Recurrent cycles of infection and inflammation contribute to lung damage and subsequent development of bronchiectasis. In the pancreas, the exocrine ducts become blocked by secretions, leading to pancreatic destruction, pancreatic enzyme insufficiency, and CF-related diabetes.
Drug and toxin-induced lung disease
Authors: Robinson Chapman
Published: May 2021

A vast number of drugs can damage the respiratory system, from nose to alveoli. All agents have equal prominence but are coded with a star rating to indicate likely prevalence. This chapter describes the commoner drugs that produce respiratory problems. Often the clinical problem is to differentiate drug toxicity from other causes of ILD.
Gastrointestinal disease and the lung
Authors: Robinson Chapman
Published: May 2021

Predominantly right-sided pleural effusion occurring in patients with liver cirrhosis and no cardiorespiratory cause for the effusion, often with minimal ascites. The ascitic fluid accumulates in the chest as a result of diaphragmatic defects. Hepatopulmonary syndrome (HPS) is the triad of chronic liver disease and portal hypertension, arteriovenous (AV) shunting in the lungs, predominantly at the bases, and subsequent ventilation-perfusion abnormalities, arterial hypoxia. Porto-pulmonary hypertension (POPH) is PAH occurring in association with liver cirrhosis and portal hypertension. The chapter also covers inflammatory bowel disease, coeliac disease, and pancreatitis.
Hypersensitivity pneumonitis
Authors: Robinson Chapman
Published: May 2021

Group of lung diseases typically caused by inhalation of organic antigen to which the individual has been previously sensitized. Disease following inhalation of inorganic antigens and drug ingestion is also reported. Hypersensitivity pneumonitis (HP; previously termed extrinsic allergic alveolitis) is often divided into ‘acute’ and ‘chronic’ forms, based on the time course of presentation. Acute HP often follows a short period of exposure to a high concentration of antigen and is usually reversible. Chronic HP typically follows a period of chronic exposure to a low antigen dose and is less reversible. These two presentations may overlap, and ‘subacute’ forms of the disease are recognized.
Lung cancer
Authors: Robinson Chapman
Published: May 2021

Includes: Epidemiology and types, clinical features, investigations, diagnostic procedures, staging, non-small cell lung cancer (NSCLC) and its surgery and systemic anti-cancer therapy, radiotherapy, small cell lung cancer (SCLC) and its treatment, emerging areas of lung cancer, the aetiology, clinical assessment, and management of superior vena caval obstruction (SVCO), hypercalcaemia, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), spinal cord compression, pulmonary carcinoid tumours, pulmonary nodules, lung cancer screening.
Mediastinal abnormalities
Authors: Robinson Chapman
Published: May 2021

The mediastinum is the area within the centre of the chest containing the heart, great vessels, nerves, lymph nodes, trachea, oesophagus, and thymus. Two-thirds of mediastinal masses are benign. These abnormalities tend to occure between the ages of 20–40 years; presence of symptoms and anterior location of a mass are all associated with an increased likelihood of malignancy. Common symptoms of mediastinal disease include cough, chest pain, and dyspnoea, as well as symptoms relating to any structure being compressed or disrupted such as dysphagia, stridor, SVCO or Horner’s syndrome. Systemic effects (night sweats, weight loss in lymphoma) and paraneoplastic effects (e.g. myasthenia with thymoma) may be seen. Mediastinal disorders can also be asymptomatic.
Respiratory infection—viral
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Influenza: background, diagnosis, and management, cytomegalovirus pneumonia, adenovirus, measles, human metapneumovirus, parainfluenza, respiratory syncytial virus, varicella pneumonia, hantavirus pulmonary syndrome, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), coronavirus (COVID-19).
Sarcoidosis
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

A multi-system disorder of unknown cause, likely resulting from the interplay of environmental and genetic factors, characterized by non-caseating granulomata and CD4+ Th1-biased T cell response in affected organs. Commonly involves the respiratory system but can affect nearly all organs. Fifty to sixty per cent of people have spontaneous remissions; others may develop chronic, and sometimes progressive, disease.
Upper airway and tracheal disease
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Acute upper airway obstruction, anaphylaxis, upper respiratory tract infections, laryngeal and tracheal disorders,
Financial entitlements
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Statutory sick pay (SSP), employment and support allowance (ESA), personal independence payment (PIP), direct payments, carer’s allowance, NHS continuing healthcare, income support ± disability premiums, working tax credit (with extra credit for disability), disabled students’ allowance (DSA), access to work grant, disabled facilities grant, other transport assistance, industrial injuries disablement benefit, reduced earning allowance.
Lung transplantation
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Patient selection, contraindications, investigations and assessment, surgical approaches, follow-up, outcomes and future developments, and complications.
Non-invasive ventilation (NIV)
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Includes: Positive pressure ventilators, CPAP, high-flow nasal oxygen (HFNO), indications, acute exacerbation of COPD, acute cardiogenic pulmonary oedema, decompensated OSA and obesity hypoventilation, respiratory failure from neuromuscular weakness, Immunocompromised patients, CAP, contraindications, chest wall deformity and neuromuscular weakness, sleep apnoea, cystic fibrosis, COPD, NIV end-of-life weaning
Palliative care
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Palliative care is defined by the World Health Organization (WHO) as an approach that improves the QoL of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification, impeccable assessment, and treatment of pain and other problems, including physical, psychosocial, and spiritual.
Pleural biopsy
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Using image guidance (either CT or US), a cutting needle takes several 1–2 cm cores along the long axis of any parietal pleural pathology. PET/CT may have a role guiding pleural biopsy in patients with diffuse pleural abnormality to increase sensitivity. US-guided pleural biopsies increase microbiological diagnosis in pleural infection but this is not routine practice. Using thoracoscopic biopsy (medical thoracoscopy/VATS), multiple biopsies are taken of visually abnormal parietal pleura. Using a pleural biopsy needle in a ‘blind’ percutaneous fashion to take multiple biopsies. Not advocated for diagnosing malignancy. May have utility in resource-limited settings for diffuse pleural diseases, but thoracoscopy still preferred.
Thoracic ultrasound (TUS)
Authors: Chapman Stephen J. , Robinson Grace V. , Shrimanker Rahul , Turnbull Chris D. , Wrightson John M.
Published: May 2021

Thoracic ultrasound (TUS) is increasingly used for bedside evaluation of the pleural space and thorax. Given improved safety, NPSA and BTS guidance ‘strongly recommend’ TUS for pleural fluid procedure site selection. TUS also gives useful diagnostic information that may alter management (e.g. a patient with a transudative effusion who has pleural nodularity, suggestive of malignancy).
CD44 alternative splicing senses intragenic DNA methylation in tumors via direct and indirect mechanisms
Authors: Batsché Eric , Yi Jia , Mauger Oriane , Kornobis Etienne , Hopkins Benjamin , Hanmer-Lloyd Charlotte , Muchardt Christian
Published: May 2021

DNA methylation (meDNA) is a modulator of alternative splicing, and splicing perturbations are involved in tumorigenesis nearly as frequently as DNA mutations. However, the impact of meDNA on tumorigenesis via splicing-mediated mechanisms has not been thoroughly explored. Here, we found that HCT116 colon carcinoma cells inactivated for the DNA methylases DNMT1/3b undergo a partial epithelial to mesenchymal transition associated with increased CD44 variant exon skipping. These skipping events are directly mediated by the loss of intragenic meDNA and the chromatin factors MBD1/2/3 and HP1γ and are also linked to phosphorylation changes in elongating RNA polymerase II. The role of meDNA in alternative splicing was confirmed by using the dCas9/DNMT3b tool. We further tested whether the meDNA level could have predictive value in the MCF10A model for breast cancer progression and in patients with acute lymphoblastic leukemia (B ALL). We found that a small number of differentially spliced genes, mostly involved in splicing and signal transduction, are correlated with the local modulation of meDNA. Our observations suggest that, although DNA methylation has multiple avenues to affect alternative splicing, its indirect effect may also be mediated through alternative splicing isoforms of these meDNA sensors.
Multivariable pattern classification differentiates relational self-esteem from personal self-esteem
Authors: Li Jiwen , Zeng Mei , Liu Mingyan , Zhao Xiaolin , Hu Weiyu , Wang Chong , Deng Chijun , Li Rong , Chen Huafu , Yang Juan
Published: May 2021

Relational self-esteem (RSE) refers to one’s sense of self-worth based on the relationship with significant others, such as family and best friends. Although previous neuroimaging research has investigated the neural processes of RSE, it is less clear how RSE is represented in multivariable neural patterns. Being able to identify a stable RSE signature could contribute to knowledge about relational self-worth. Here, using multivariate pattern classification to differentiate RSE from personal self-esteem (PSE), which pertains to self-worth derived from personal attributes, we obtained a stable diagnostic signature of RSE relative to PSE. We found that multivariable neural activities in the superior/middle temporal gyrus, precuneus, posterior cingulate cortex, dorsal medial Prefrontal Cortex (dmPFC) and temporo-parietal junction were responsible for diagnosis of RSE, suggesting that the evaluation of RSE involves the retrieval of relational episodic memory, perspective-taking and value calculation. Further, these diagnostic neural signatures were able to sensitively decode neural activities related to RSE in another independent test sample, indicating the reliability of the brain state represented. By providing a reliable multivariate brain pattern for RSE relative to PSE, our results informed more cognitively prominent processing of RSE than that of PSE and enriched our knowledge about how relational self-worth is generated in the brain.
Development and dissemination of a consumer health information website on infant and toddler sleep
Authors: Mindell Jodi A , Leichman Erin S , Walters Russel , Bhullar Bula
Published: May 2021

Sleep problems are prevalent in early childhood, with the majority of caregivers desiring to change something about their child’s sleep. Quality-assured education and resources are needed to be related to infant and toddler sleep. This article describes the development and dissemination of a global consumer health information website (http://www.babysleep.com) by the Pediatric Sleep Council to provide publicly accessible evidence-based information and resources for caregivers and practitioners. The website includes sleep health-related information and resources. Three phases, including the launch, social media strategy, and search engine optimization, for promotion and dissemination of the site was implemented. Analysis of dissemination indicates exponential growth of the site since its launch. With access across the globe, the site has developed from its inception into a widely-used resource, with over 800,000 users from around the world (99% of countries).
Mobile health use predicts self-efficacy and self-management in adolescents with sickle cell disease
Authors: Hood Anna M , Nwankwo Cara , Walton Ashley , McTate Emily , Joffe Naomi , Quinn Charles T , Britto Maria T , Peugh James , Mara Constance A , Crosby Lori E
Published: May 2021

Sickle cell disease (SCD) is associated with significant health challenges that often worsen during adolescence. Living with SCD requires a substantial amount of self-management and mobile health (mHealth) holds considerable promise for assessing and changing behaviors to improve health outcomes. We integrated a mobile app as an adjunct to a group intervention (SCThrive) and hypothesized that more engagement with the mHealth app would increase self-management and self-efficacy for adolescents and young adults (AYA) with SCD. Twenty-six AYA ages 13–21 years (54% female; 46% HbSS genotype; all African-American/Black) received six weekly group sessions (three in-person, three online). Participants were provided with the mobile app (iManage for SCD) to record progress on their self-management goals and log pain and mood symptoms. The Transition Readiness Assessment Questionnaire (TRAQ-5) assessed self-management skills and the Patient Activation Measure (PAM-13) assessed self-efficacy at baseline and post-treatment. Logging on to the app more frequently was associated higher mood ratings (r = .54, CI[.18, .77], p = .006) and lower pain ratings (r = −.48, CI[−.77, −.02], p = .04). Regression analyses demonstrated that after controlling for scores at baseline, the number of logins to the app predicted self-management skills (p = .05, η2 = .17) and possibly self-efficacy (p = .08, η2 = .13). Our study findings indicate that it can be challenging to maintain engagement in mHealth for AYA with SCD, but for those who do engage, there are significant benefits related to self-management, self-efficacy, and managing pain and mood.
Encephalitis Associated With Immune Checkpoint Inhibitor Treatment in Patients With Melanoma
Authors: Martínez-Vila Clara , Laguna Juan C. , Segui Elia , Ruiz Gustavo , Aya Moreno Francisco , Fernandez-Morales Luis M. , Giner Joaquim Julia , Padrosa Joan , Fernandez Laia , Gaba Lydia , Victoria Ivan , Arance Fernandez Ana.M.
Published: May 2021

Since the approval of immune checkpoint anti–programmed cell death protein 1 antibodies (pembrolizumab and nivolumab) and anti–cytotoxic T-lymphocyte–associated protein 4 (ipilimumab) in combination or monotherapy, significant advances have been made in the treatment of metastatic melanoma. The nonspecific immune stimulation resulting from these drugs can case a wide range of side effects in many organs including the nervous system, named immune-related adverse events. Few immune-related encephalitis associated with these antibodies have been described in the literature. It is a rare complication (<1% of the total of immune-related adverse events) but it can be fatal if not diagnosed and treated on time. We describe 3 cases of patients with melanoma, which were treated with a combination of ipilimumab-nivolumab (case 1), ipilimumab monotherapy (case 2), and nivolumab monotherapy (case 3), who developed an encephalitis which was related to immune checkpoint therapy.
Day of surgery capillary glucose predictability of complications and length of stay for total knee arthroplasty patients with diabetes: a retrospective cohort study
Authors: Robin Alex , Gautreau Sylvia , MacSween Mary C. , Cartier Louis-Jacques
Published: May 2021

Background:

The aim of this study is to determine if the day of surgery capillary blood glucose readings predict complications and length of stay (LOS) in patients with diabetes undergoing total knee arthroplasty (TKA).

Methods:

Patients 45 years and above with diabetes who had a primary TKA between April 2015 and April 2019 at The Moncton Hospital were identified using our discharge database. Using patient charts, study variables collected included day of surgery capillary blood glucose, demographic information, Charlson Comorbidity Index, surgery indication, American Society of Anesthesiologists score, diabetes management, complications within 90 days (urinary tract infection, acute kidney injury, wound infection, bleed, venous thromboembolism) and LOS.

Results:

The area under the receiver operating characteristic curve for a day of surgery capillary glycemia prediction of LOS was 0.578 (95% confidence interval: 0.491-0.664) with a P-value of 0.063, which was not statistically significant. The receiver operating characteristic curve for postoperative complications prediction by day of surgery capillary blood glucose was 0.564 (95% confidence interval: 0.426-0.701) with a P-value of 0.319, which was not statistically significant. Routine preoperative A1C and random glucose were predictive of the day of surgery glucose.

Conclusions:

Preoperative A1C and random glucose were predictive of the day of surgery capillary glucose in elective TKA surgeries. There was no association between preoperative capillary glucose and complications or LOS. Since current recommendations are variable and largely empiric, there is a need for a randomized-controlled study of preoperative diabetes management, particularly for orthopedic surgeries. This could minimize procedure delays and reduce morbidity and mortality for patients.
Genetic diversity through social heterosis can increase virulence in RNA viral infections and cancer progression
Authors: Ebrahimi Saba , Nonacs Peter
Published: May 2021

In viral infections and cancer tumours, negative health outcomes often correlate with increasing genetic diversity. Possible evolutionary processes for such relationships include mutant lineages escaping host control or diversity,
per se
, creating too many immune system targets. Another possibility is social heterosis where mutations and replicative errors create clonal lineages varying in intrinsic capability for successful dispersal; improved environmental buffering; resource extraction or effective defence against immune systems. Rather than these capabilities existing in one genome, social heterosis proposes complementary synergies occur across lineages in close proximity. Diverse groups overcome host defences as interacting ‘social genomes’ with group genetic tool kits exceeding limited individual plasticity. To assess the possibility of social heterosis in viral infections and cancer progression, we conducted extensive literature searches for examples consistent with general and specific predictions from the social heterosis hypothesis. Numerous studies found supportive patterns in cancers across multiple tissues and in several families of RNA viruses. In viruses, social heterosis mechanisms probably result from long coevolutionary histories of competition between pathogen and host. Conversely, in cancers, social heterosis is a by-product of recent mutations. Investigating how social genomes arise and function in viral quasi-species swarms and cancer tumours may lead to new therapeutic approaches.
Short branch cut approximation in two-dimensional hydrodynamics with free surface
Authors: Dyachenko A. I. , Dyachenko S. A. , Lushnikov P. M. , Zakharov V. E.
Published: May 2021

A potential motion of ideal incompressible fluid with a free surface and infinite depth is considered in two-dimensional geometry. A time-dependent conformal mapping of the lower complex half-plane of the auxiliary complex variable
w
into the area filled with fluid is performed with the real line of
w
mapped into the free fluid’s surface. The fluid dynamics can be fully characterized by the motion of the complex singularities in the analytical continuation of both the conformal mapping and the complex velocity. We consider the short branch cut approximation of the dynamics with the small parameter being the ratio of the length of the branch cut to the distance between its centre and the real line of
w
. We found that the fluid dynamics in that approximation is reduced to the complex Hopf equation for the complex velocity coupled with the complex transport equation for the conformal mapping. These equations are fully integrable by characteristics producing the infinite family of solutions, including moving square root branch points and poles. These solutions involve practical initial conditions resulting in jets and overturning waves. The solutions are compared with the simulations of the fully nonlinear Eulerian dynamics giving excellent agreement even when the small parameter approaches about one.
Incomplete reproductive isolation and strong transcriptomic response to hybridization between sympatric sister species of salmon
Authors: McKenzie Jessica L. , Araújo H. Andrés , Smith Jack L. , Schluter Dolph , Devlin Robert H.
Published: May 2021

Global change is altering ecosystems at an unprecedented rate. The resulting shifts in species ranges and reproductive timing are opening the potential for hybridization between closely related species which could dramatically alter the genetic diversity, adaptive capacity and evolutionary trajectory of interbreeding taxa. Here, we used behavioural breeding experiments,
in vitro
fertilization experiments, and whole-transcriptome gene expression data to assess the potential for and consequences of hybridization between Chinook and Coho salmon. We show that behavioural and gametic prezygotic barriers between socio-economically valuable Chinook and Coho salmon are incomplete. Postzygotically, we demonstrate a clear transcriptomic response to hybridization among F
1
Chinook-Coho offspring. Genes transgressively expressed within hybrids were significantly enriched with genes encoded in the nucleus but localized to the mitochondrion, suggesting a potential role for mito-nuclear incompatibilities as a postzygotic mechanism of hybrid breakdown. Chinook and Coho salmon are expected to continue to respond to climate change with shifts in migration timing and habitat use, potentiating hybridization between these species. The downstream consequences of hybridization on the future of these threatened salmon, and the ecosystems they inhabit, is unknown.
Fossils improve phylogenetic analyses of morphological characters
Authors: Mongiardino Koch Nicolás , Garwood Russell J. , Parry Luke A.
Published: May 2021

Fossils provide our only direct window into evolutionary events in the distant past. Incorporating them into phylogenetic hypotheses of living clades can help time-calibrate divergences, as well as elucidate macroevolutionary dynamics. However, the effect fossils have on phylogenetic reconstruction from morphology remains controversial. The consequences of explicitly incorporating the stratigraphic ages of fossils using tip-dated inference are also unclear. Here, we use simulations to evaluate the performance of inference methods across different levels of fossil sampling and missing data. Our results show that fossil taxa improve phylogenetic analysis of morphological datasets, even when highly fragmentary. Irrespective of inference method, fossils improve the accuracy of phylogenies and increase the number of resolved nodes. They also induce the collapse of ancient and highly uncertain relationships that tend to be incorrectly resolved when sampling only extant taxa. Furthermore, tip-dated analyses under the fossilized birth–death process outperform undated methods of inference, demonstrating that the stratigraphic ages of fossils contain vital phylogenetic information. Fossils help to extract true phylogenetic signals from morphology, an effect that is mediated by both their distinctive morphology and their temporal information, and their incorporation in total-evidence phylogenetics is necessary to faithfully reconstruct evolutionary history.
Repeated loss of variation in insect ovary morphology highlights the role of development in life-history evolution
Authors: Church Samuel H. , de Medeiros Bruno A. S. , Donoughe Seth , Márquez Reyes Nicole L. , Extavour Cassandra G.
Published: May 2021

The number of offspring an organism can produce is a key component of its evolutionary fitness and life history. Here we perform a test of the hypothesized trade-off between the number and size of offspring using thousands of descriptions of the number of egg-producing compartments in the insect ovary (ovarioles), a common proxy for potential offspring number in insects. We find evidence of a negative relationship between egg size and ovariole number when accounting for adult body size. However, in contrast to prior claims, we note that this relationship is not generalizable across all insect clades, and we highlight several factors that may have contributed to this size-number trade-off being stated as a general rule in previous studies. We reconstruct the evolution of the arrangement of cells that contribute nutrients and patterning information during oogenesis (nurse cells), and show that the diversification of ovariole number and egg size have both been largely independent of their presence or position within the ovariole. Instead, we show that ovariole number evolution has been shaped by a series of transitions between variable and invariant states, with multiple independent lineages evolving to have almost no variation in ovariole number. We highlight the implications of these invariant lineages on our understanding of the specification of ovariole number during development, as well as the importance of considering developmental processes in theories of life-history evolution.
Multi-level social organization and nest-drifting behaviour in a eusocial insect
Authors: Lengronne Thibault , Mlynski David , Patalano Solenn , James Richard , Keller Laurent , Sumner Seirian
Published: May 2021

Stable social groups usually consist of families. However, recent studies have revealed higher level social structure, with interactions between family groups across different levels of social organization in multiple species. The explanations for why this apparently paradoxical behaviour arises appear to be varied and remain untested. Here, we use automated radio-tagging data from over 1000 wasps from 93 nests and social network analyses of over 30 000 nest visitation records to describe and explain interactions across levels of social organization in the eusocial paper waspPolistes canadensis. We detected three levels of social organization (nest, aggregation and community) which exchange ‘drifter’ individuals within and between levels. The highest level (community) may be influenced by the patchiness of high-quality nesting habitats in which these insects exist. Networks of drifter movements were explained by the distance between nests, the group size of donor nests and the worker-to-brood ratios on donor and recipient nests. These findings provide some explanation for the multi-level social interactions, which may otherwise seem paradoxical. Fitness benefits across multiple levels of social organization should be considered when trying to understand animal societies.
Host and parasite traits predict cross-species parasite acquisition by introduced mammals
Authors: Schatz Annakate M. , Park Andrew W.
Published: May 2021

Species invasions and range shifts can lead to novel host–parasite communities, but we lack general rules on which new associations are likely to form. While many studies examine parasite sharing among host species, the directionality of transmission is typically overlooked, impeding our ability to derive principles of parasite acquisition. Consequently, we analysed parasite records from the non-native ranges of 11 carnivore and ungulate species. Using boosted regression trees, we modelled parasite acquisition within each zoogeographic realm of a focal host's non-native range, using a suite of predictors characterizing the parasites themselves and the host community in which they live. We found that higher parasite prevalence among established hosts increases the likelihood of acquisition, particularly for generalist parasites. Non-native host species are also more likely to acquire parasites from established host species to which they are closely related; however, the acquisition of several parasite groups is biased to phylogenetically specialist parasites, indicating potential costs of parasite generalism. Statistical models incorporating these features provide an accurate prediction of parasite acquisition, indicating that measurable host and parasite traits can be used to estimate the likelihood of new host–parasite associations forming. This work provides general rules to help anticipate novel host–parasite associations created by climate change and other anthropogenic influences.
LENZILUMAB EFFICACY AND SAFETY IN NEWLY HOSPITALIZED COVID-19 SUBJECTS: RESULTS FROM THE LIVE-AIR PHASE 3 RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL
Authors: Temesgen Zelalem , Burger Charles D. , Baker Jason , Polk Christopher , Libertin Claudia , Kelley Colleen , Marconi Vincent C. , Orenstein Robert , Durrant Cameron , Chappell Dale , Ahmed Omar , Chappell Gabrielle , Badley Andrew D.
Published: May 2021

BACKGROUND

Severe COVID-19 pneumonia results from a hyperinflammatory immune response (cytokine storm, CS), characterized by GM-CSF mediated activation and trafficking of myeloid cells, leading to elevation of downstream inflammatory chemokines (MCP-1, IL-8, IP-10), cytokines (IL-6, IL-1), and other markers of systemic inflammation (CRP, D-dimer, ferritin). CS leads to fever, hypotension, coagulopathy, respiratory failure, ARDS, and death. Lenzilumab is a novel Humaneered® anti-human GM-CSF monoclonal antibody that directly binds GM-CSF and prevents signaling through its receptor. The LIVE-AIR Phase 3 randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of lenzilumab to assess the potential for lenzilumab to improve the likelihood of ventilator-free survival (referred to herein as survival without ventilation, SWOV), beyond standard supportive care, in hospitalized subjects with severe COVID-19.

METHODS

Subjects with COVID-19 (n=520), ≥18 years, and ≤94% oxygen saturation on room air and/or requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized to receive lenzilumab (600 mg, n=261) or placebo (n=259) via three intravenous infusions administered 8 hours apart. Subjects were followed through Day 28 following treatment.

RESULTS

Baseline demographics were comparable between the two treatment groups: male, 64.7%; mean age, 60.5 years; mean BMI, 32.5 kg/m2; mean CRP, 98.36 mg/L; CRP was <150 mg/L in 77.9% of subjects. The most common comorbidities were obesity (55.1%), diabetes (53.4%), chronic kidney disease (14.0%), and coronary artery disease (13.6%). Subjects received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the likelihood of SWOV by 54% in the mITT population (HR: 1.54; 95%CI: 1.02-2.31, p=0.041) and by 90% in the ITT population (HR: 1.90; 1.02-3.52, nominal p=0.043) compared to placebo. SWOV also relatively improved by 92% in subjects who received both corticosteroids and remdesivir (1.92; 1.20-3.07, nominal p=0.0067); by 2.96-fold in subjects with CRP<150 mg/L and age <85 years (2.96; 1.63–5.37, nominal p=0.0003); and by 88% in subjects hospitalized ≤2 days prior to randomization (1.88; 1.13-3.12, nominal p=0.015). Survival was improved by 2.17-fold in subjects with CRP<150 mg/L and age <85 years (2.17; 1.04-4.54, nominal p=0.040).

CONCLUSION

Lenzilumab significantly improved SWOV in hospitalized, hypoxic subjects with COVID-19 pneumonia over and above treatment with remdesivir and/or corticosteroids. Subjects with CRP<150 mg/L and age <85 years demonstrated an improvement in survival and had the greatest benefit from lenzilumab. NCT04351152
Male-Female Disparities in Years of Potential Life Lost Attributable to COVID-19 in the United States: A State-by-State Analysis
Authors: Xu Jay J. , Chen Jarvis T. , Belin Thomas R. , Brookmeyer Ronald S. , Suchard Marc A. , Ramirez Christina M.
Published: May 2021

Males are at higher risk relative to females of severe outcomes following COVID-19 infection. Focusing on COVID-19-attributable mortality in the United States (U.S.), we quantify and contrast years of potential life lost (YPLL) attributable to COVID-19 by sex based on data from the U.S. National Center for Health Statistics as of 31 March 2021, specifically by contrasting male and female percentages of total YPLL with their respective percent population shares and calculating age-adjusted male-to-female YPLL rate ratios both nationally and for each of the 50 states and the District of Columbia. Using YPLL before age 75 to anchor comparisons between males and females and a novel Monte Carlo simulation procedure to perform estimation and uncertainty quantification, our results reveal a near-universal pattern across states of higher COVID-19-attributable YPLL among males compared to females. Furthermore, the disproportionately high COVID-19 mortality burden among males is generally more pronounced when measuring mortality in terms of YPLL compared to age-irrespective death counts, reflecting dual phenomena of males dying from COVID-19 at higher rates and at systematically younger ages relative to females. The U.S. COVID-19 epidemic also offers lessons underscoring the importance of a public health environment that recognizes sex-specific needs as well as different patterns in risk factors, health behaviors, and responses to interventions between men and women. Public health strategies incorporating focused efforts to increase COVID-19 vaccinations among men are particularly urged.
A CRISPR interference screen reveals a role for cell wall teichoic acids in conjugation inBacillus subtilis
Authors: Harden M. Michael , Grossman Alan D.
Published: May 2021

Conjugative elements are widespread in bacteria and include plasmids and integrative and conjugative elements (ICEs). They transfer from donor to recipient cells via an element-encoded type IV secretion system. These elements interact with and utilize host functions for their lifecycles. We sought to identify essential host genes involved in the lifecycle of the integrative and conjugative element ICEBs1ofBacillus subtilis. We constructed a library of strains for inducible knockdown of essentialB. subtilisgenes using CRISPR interference. Each strain expressed one guide RNA in ICEBs1. We induced partial interference of essential genes and identified those that caused an acute defect in acquisition of ICEBs1by recipient cells. This screen revealed that reducing expression of genes needed for synthesis of cell wall teichoic acids caused a decrease in conjugation. Using three different ways to reduce their synthesis, we found that wall teichoic acids were necessary in both donors and recipients for efficient conjugative transfer of ICEBs1. Further, we found that depletion of wall teichoic acids caused cells involved in ICEBs1conjugation to die, most likely from damage to the cell envelope. Our results indicate that wall teichoic acids help protect against envelope stress caused by an active conjugation machinery.