bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging in Sjögren’s syndrome
Authors: Adams Ashok 
Published: May 2021

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
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

Abstract
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

Abstract
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

Abstract
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

AbstractSickle 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.
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.
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

ABSTRACTBACKGROUNDSevere 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.METHODSSubjects 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.RESULTSBaseline 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).CONCLUSIONLenzilumab 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

AbstractMales 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

SummaryConjugative 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.
ORAI1 establishes resistance to SARS-CoV-2 infection by regulating tonic type I interferon signaling
Authors: Wu Beibei , Ramaiah Arunachalam , Garcia Gustavo , Gwack Yousang , Arumugaswami Vaithilingaraja , Srikanth Sonal 
Published: May 2021

AbstractORAI1 and STIM1 are the critical mediators of store-operated Ca2+entry by acting as the pore subunit and an endoplasmic reticulum-resident signaling molecule, respectively. In addition to Ca2+signaling, STIM1 is also involved in regulation of a cytosolic nucleic acid sensing pathway. UsingORAI1andSTIM1knockout cells, we examined their contribution to the host response to SARS-CoV-2 infection.STIM1knockout cells showed strong resistance to SARS-CoV-2 infection due to enhanced type I interferon response. On the contrary,ORAI1knockout cells showed high susceptibility to SARS-CoV-2 infection as judged by increased expression of viral proteins and a high viral load. Mechanistically,ORAI1knockout cells showed reduced homeostatic cytoplasmic Ca2+concentration and severe impairment in tonic interferon signaling. Transcriptome analysis showed downregulation of multiple cellular defense mechanisms, including antiviral signaling pathways in ORAI1 knockout cells, which are likely due to reduced expression of the Ca2+-dependent transcription factors of the activator protein 1 (AP-1) family andMEF2C. Our results identify a novel role of ORAI1-mediated Ca2+signaling in regulating the baseline type I interferon level, which is a determinant of host resistance to SARS-CoV-2 infection.