bluuebunny/crossref_metadata_2025_split huggingface dataset:
A journey through the lectin pathway of complement—MBL and beyond
Authors: Garred Peter , Genster Ninette , Pilely Katrine , Bayarri‐Olmos Rafael , Rosbjerg Anne , Ma Ying Jie , Skjoedt Mikkel‐Ole 
Published: October 2016

SummaryMannose‐binding lectin (MBL), collectin‐10, collectin‐11, and the ficolins (ficolin‐1, ficolin‐2, and ficolin‐3) are soluble pattern recognition molecules in the lectin complement pathway. These proteins act as mediators of host defense and participate in maintenance of tissue homeostasis. They bind to conserved pathogen‐specific structures and altered self‐antigens and form complexes with the pentraxins to modulate innate immune functions. All molecules exhibit distinct expression in different tissue compartments, but all are found to a varying degree in the circulation. A common feature of these molecules is their ability to interact with a set of serine proteases named MASPs (MASP‐1, MASP‐2, and MASP‐3). MASP‐1 and ‐2 trigger the activation of the lectin pathway and MASP‐3 may be involved in the activation of the alternative pathway of complement. Furthermore, MASPs mediate processes related to coagulation, bradykinin release, and endothelial and platelet activation. Variant alleles affecting expression and structure of the proteins have been associated with a variety of infectious and non‐infectious diseases, most commonly as disease modifiers. Notably, the severe 3MC (Malpuech, Michels, Mingarelli, and Carnevale) embryonic development syndrome originates from rare mutations affecting either collectin‐11 or MASP‐3, indicating a broader functionality of the complement system than previously anticipated. This review summarizes the characteristics of the molecules in the lectin pathway.
The complement and contact activation systems: partnership in pathogenesis beyond angioedema
Authors: Ghebrehiwet Berhane , Kaplan Allen P. , Joseph Kusumam , Peerschke Ellinor I. B. 
Published: October 2016

SummaryThe blood plasma contains four biologically important proteolytic cascades, which probably evolved from the same ancestral gene. This in part may explain why each cascade has very similar “initiating trigger” followed by sequential and cascade‐like downstream enzymatic activation pattern. The four cascades are: the complement system, the blood clotting cascade, the fibrinolytic system, and the kallikrein‐kinin system. Although much has been written about the interplay between all these enzymatic cascades, the cross‐talk between the complement and the kinin generating systems has become particularly relevant as this interaction results in the generation of nascent molecules that have significant impact in various inflammatory diseases including angioedema and cancer. In this review, we will focus on the consequences of the interplay between the two systems by highlighting the role of a novel molecular link called gC1qR. Although this protein was first identified as a receptor for C1q, it is now recognized as a multiligand binding cellular protein, which serves not only as C1q receptor, but also as high affinity (KD ≤ 0.8 nM) binding site for both high molecular weight kininogen (HK) and factor XII (FXII). At inflammatory sites, where atherogenic factors such as immune complexes and/or pathogens can activate the endothelial cell into a procoagulant and proinflammatory surface, the two pathways are activated to generate vasoactive peptides that contribute in various ways to the inflammatory processes associated with numerous diseases. More importantly, since recent observations strongly suggest an important role for both pathways in cancer, we will focus on how a growing tumor cluster can employ the byproducts derived from the two activation systems to ensure not only its survival and growth, but also its escape into distal sites of colonization.
Injury site‐specific targeting of complement inhibitors for treating stroke
Authors: Alawieh Ali , Tomlinson Stephen 
Published: October 2016

SummaryCumulative evidence indicates a role for the complement system in both pathology and recovery after ischemic stroke. Here, we review the current understanding of the dual role of complement in poststroke injury and recovery, and discuss the challenges of anti‐complement therapies. Most complement directed therapeutics currently under investigation or development systemically inhibit the complement system, but since complement is important for immune surveillance and is involved in various homeostatic activities, there are potential risks associated with systemic inhibition. Depending on the target within the complement pathway, other concerns are high concentrations of inhibitor required, low efficacy and poor bioavailability. To overcome these limitations, approaches to target complement inhibitors to specific sites have been investigated. Here, we discuss targeting strategies, with a focus on strategies developed in our lab, to specifically localize complement inhibition to sites of tissue injury and complement activation, and in particular to the postischemic brain. We discuss various injury site‐specific targeted complement inhibitors as potential therapeutic agents for the treatment of ischemic stroke treatment, as well as their use as investigative tools for probing complement‐dependent pathophysiological processes.
Endothelial cells: source, barrier, and target of defensive mediators
Authors: Roumenina Lubka T. , Rayes Julie , Frimat Marie , Fremeaux‐Bacchi Veronique 
Published: October 2016

SummaryEndothelium is strategically located at the interface between blood and interstitial tissues, placing thus endothelial cell as a key player in vascular homeostasis. Endothelial cells are in a dynamic equilibrium with their environment and constitute concomitantly a source, a barrier, and a target of defensive mediators. This review will discuss the recent advances in our understanding of the complex crosstalk between the endothelium, the complement system and the hemostasis in health and in disease. The first part will provide a general introduction on endothelial cells heterogeneity and on the physiologic role of the complement and hemostatic systems. The second part will analyze the interplay between complement, hemostasis and endothelial cells in physiological conditions and their alterations in diseases. Particular focus will be made on the prototypes of thrombotic microangiopathic disorders, resulting from complement or hemostasis dysregulation‐mediated endothelial damage: atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Novel aspects of the pathophysiology of the thrombotic microangiopathies will be discussed.
The immune system's role in sepsis progression, resolution, and long‐term outcome
Authors: Delano Matthew J. , Ward Peter A. 
Published: October 2016

SummarySepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis‐induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti‐inflammatory responses. With advances in intensive care medicine and goal‐directed interventions, early 30‐day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. As so many sepsis survivors succumb later to persistent, recurrent, nosocomial, and secondary infections, many investigators have turned their attention to the long‐term sepsis‐induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis‐associated immune cell defects correlate with long‐term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long‐term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long‐term sepsis mortality.
Safety and Clinical Outcomes of Catheter Ablation of Atrial Fibrillation in Patients With Chronic Kidney Disease
Authors: ULLAL ADITYA J. , KAISER DANIEL W. , FAN JUN , SCHMITT SUSAN K. , THAN CLAIRE T. , WINKELMAYER WOLFGANG C. , HEIDENREICH PAUL A. , PICCINI JONATHAN P. , PEREZ MARCO V. , WANG PAUL J. , TURAKHIA MINTU P. 
Published: October 2016

Catheter Ablation of AF in Chronic Kidney DiseaseIntroductionData regarding catheter ablation of atrial fibrillation (AF) in patients with chronic kidney disease (CKD) is limited. We therefore assessed the association of CKD with common safety and clinical outcomes in a nationwide sample of ablation recipients.MethodsUsing MarketScan® Commercial Claims and Medicare Supplemental Databases, we evaluated 30‐day safety and 1‐year clinical outcomes in patients who underwent a first AF ablation procedure between 2007 and 2011. We calculated frequency of common 30‐day complications and calculated frequencies, incidence rates, and Cox proportional hazards for outcomes at 1‐year postablation.ResultsOf 21,091 patients included, 1,593 (7.6%) had CKD. Patients with CKD were older (64 years vs. 59 years, P < 0.001) with higher CHA2DS2‐VASc scores (3.2 vs. 1.8, P < 0.001). At 30 days postablation, patients with CKD had similar rates of stroke/TIA (0.13% vs. 0.13%, P = 0.99), perforation/tamponade (3.2% vs. 3.1%, P = 0.83), and vascular complications (2.4% vs. 2.2%, P = 0.59) as patients without CKD, but were more likely to be hospitalized for heart failure (2.1% vs. 0.4%, P < 0.001). In multivariate analysis, there were no significant differences in hazards of AF hospitalization (adjusted HR: 1.02, 95%CI: 0.87–1.20), cardioversion (adjusted HR: 0.99, 95%CI: 0.87–1.12), or repeat AF ablation (adjusted HR: 0.89, 95%CI: 0.76–1.06) at 1 year.ConclusionsAmong patients selected for AF ablation, those with and without CKD had similar rates of postprocedural complications although they were more likely to be re‐admitted for heart failure. CKD was not independently associated with AF hospitalization, cardioversion, and repeat ablation. These findings can inform clinical decision‐making in patients with AF and CKD.
HULC: an oncogenic long non‐coding RNA in human cancer
Authors: Yu Xin , Zheng Heyi , Chan Matthew T.V. , Wu William Ka Kei 
Published: October 2016

AbstractHighly up‐regulated in liver cancer (HULC) was originally identified as the most overexpressed long non‐coding RNA in hepatocellular carcinoma. Since its discovery, the aberrant up‐regulation of HULC has been demonstrated in other cancer types, including gastric cancer, pancreatic cancer, osteosarcoma and hepatic metastasis of colorectal cancer. Recent discoveries have also shed new light on the upstream molecular mechanisms underlying HULC deregulation. As an oncogene, HULC promotes tumorigenesis by regulating multiple pathways, such as down‐regulation of EEF1E1, promotion of abnormal lipid metabolism, and up‐regulation of sphingosine kinase 1. Pertinent to clinical practice, a genetic variant in the HULC gene has been found to alter the risk for hepatocellular carcinoma and oesophageal cancer, whereas cancer patients with high or low expression of HULC exhibit different clinical outcome. These findings highlighted the pathogenic role and clinical utility of HULC in human cancers. Further efforts are warranted to promote the development of HULC‐directed therapeutics.
HFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: A genotype‐stratified cohort study of hemochromatosis in Australian women
Authors: Warne Charles D , Zaloumis Sophie G , Bertalli Nadine A , Delatycki Martin B , Nicoll Amanda J , McLaren Christine E , Hopper John L , Giles Graham G , Anderson Greg J , Olynyk John K , Powell Lawrie W , Allen Katrina J , Gurrin Lyle C ,   for the HealthIron Study Investigators
Published: October 2016

AbstractBackground and AimWomen who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload‐related disease than p.C282Y homozygous men, presumably because of the iron‐depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p.C282Y nor p.H63D mutations (HFE wild types) as comparison groups.MethodsA sample of the Melbourne Collaborative Cohort Study was selected for the “HealthIron” study (n = 1438) including all HFE p.C282Y homozygotes plus a random sample stratified by HFE‐genotype (p.C282Y and p.H63D). The relationship between the natural logarithm of SF and time since menopause was examined using linear mixed models incorporating spline smoothing.ResultsFor p.C282Y homozygotes, SF increased by a factor of 3.6 (95% CI (1.8, 7.0), P < 0.001) during the first 10 years postmenopause, after which SF continued to increase but at less than half the previous rate. In contrast, SF profiles for other HFE genotype groups increase more gradually and did not show a distinction between premenopausal and postmenopausal SF levels. Only p.C282Y homozygotes had predicted SF exceeding 200 μg/L postmenopause, but the projected SF did not increase the risk of iron overload‐related disease.ConclusionsThese data provide the first documented evidence that physiological blood loss is a major factor in determining the marked gender difference in expression of p.C282Y homozygosity.
The Patient Health Questionnaire‐9 as a Screening Tool for Depression in Individuals with Type 2 Diabetes Mellitus: The Maastricht Study
Authors: Janssen Eveline P. C. J. , Köhler Sebastian , Stehouwer Coen D. A. , Schaper Nicolaas C. , Dagnelie Pieter C. , Sep Simone J. S. , Henry Ronald M. A. , van der Kallen Carla J. H. , Verhey Frans R. , Schram Miranda T. 
Published: October 2016

ObjectivesTo assess the psychometric properties and identify the best cutoff value of the Patient Health Questionnaire‐9 (PHQ‐9) for depression screening in individuals with type 2 diabetes mellitus (T2DM).DesignObservational population‐based cohort study.SettingThe Maastricht Study.ParticipantsIndividuals with and without T2DM (mean age 58.6 ± 8.1, 44.6% male) according to an oral glucose tolerance test (N = 2,997).MeasurementsDepressive disorder and depressive symptoms were measured using the Mini‐International Neuropsychiatric Interview (MINI) as the reference and the PHQ‐9. Cronbach alpha, Cohen's kappa and receiver operating characteristic (ROC) analyses were used. Differences in factorial structure between participants with and without T2DM were tested using multigroup confirmatory factor analysis.ResultsBased on the traditional PHQ‐9 cutoff value, 133 (4.4%) participants had depressive symptoms (PHQ‐9 score ≥10). Internal consistency of the PHQ‐9 was good (Cronbach α = 0.87 with T2DM, 0.82 without T2DM), the kappa of agreement between the PHQ‐9 and the MINI was moderate (0.40 with T2DM, 0.43 without T2DM). Area under the ROC curve for the PHQ‐9 was 0.87 in participants with T2DM and 0.88 in those without. A PHQ‐9 cutoff score of 5 provided the best sensitivity (92.3%), with acceptable specificity (70.4%), for T2DM, similar to sensitivity and specificity in individuals without T2DM. Factor analysis suggested a similar two‐factor structure in both groups (affective and somatic symptoms).ConclusionPatient Health Questionnaire‐9 performs well as a screening tool for depressive symptoms in individuals with and without T2DM based on the cutoff value of 5, indicating that the PHQ‐9 can be used in two‐stage screening in primary care to select individuals with T2DM for further psychological evaluation.
Frailty Levels in Residential Aged Care Facilities Measured Using the Frailty Index and FRAIL‐NH Scale
Authors: Theou Olga , Tan Edwin C.K. , Bell J. Simon , Emery Tina , Robson Leonie , Morley John E. , Rockwood Kenneth , Visvanathan Renuka 
Published: October 2016

ObjectivesTo compare the FRAIL‐NH scale with the Frailty Index in assessing frailty in residential aged care facilities.DesignCross‐sectional.SettingSix Australian residential aged care facilities.ParticipantsIndividuals aged 65 and older (N = 383, mean aged 87.5 ± 6.2, 77.5% female).MeasurementsFrailty was assessed using the 66‐item Frailty Index and the FRAIL‐NH scale. Other measures examined were dementia diagnosis, level of care, resident satisfaction with care, nurse‐reported resident quality of life, neuropsychiatric symptoms, and professional caregiver burden.ResultsThe FRAIL‐NH scale was significantly associated with the Frailty Index (correlation coefficient = 0.81, P < .001). Based on the Frailty Index, 60.8% of participants were categorized as frail and 24.4% as most frail. Based on the FRAIL‐NH, 37.5% of participants were classified as frail and 35.9% as most frail. Women were assessed as being frailer than men using both tools (P = .006 for FI; P = .03 for FRAIL‐NH). Frailty Index levels were higher in participants aged 95 and older (0.39 ± 0.13) than in those aged younger than 85 (0.33 ± 0.13; P = .008) and in participants born outside Australia (0.38 ± 0.13) than in those born in Australia (0.34 ± 0.13; P = .01). Both frailty tools were associated with most characteristics that would indicate higher care needs, with the Frailty Index having stronger associations with all of these measures.ConclusionThe FRAIL‐NH scale is a simple and practical method to screen for frailty in residential aged care facilities.
Age Differences in Sequential Speech Production: Articulatory and Physiological Factors
Authors: Bilodeau‐Mercure Mylène , Tremblay Pascale 
Published: October 2016

ObjectivesTo explore age differences in speech production in relation to orofacial physiology.DesignCross‐sectional quasi‐experimental group study.SettingGeneral community.ParticipantsPhysically and cognitively healthy volunteers recruited from the community (N = 30), including 15 young (18–39) and 15 older (66–85) adults.MeasurementsAccuracy and speech rate were calculated during the production of sequences of syllables containing oral vowels, nasal vowels, or both. Lip and tongue muscular strength, muscular endurance, and tactile sensitivity were also measured.ResultsOlder adults had a slower speech rate than younger adults and greater difficulty articulating nasal vowels. Analyses revealed that age‐related decline in lip endurance is associated with decline in accuracy during speech production.ConclusionOlder adults are not just slower than younger adults, they also exhibit specific articulatory difficulties. Although many physiological changes in orofacial functions occur in aging, only muscular endurance of the lips is related to age‐related differences in speech production. This information is important for the development of speech interventions targeting older adults with speech motor disorders.
Fear of Falling in Older Mexican Americans: A Longitudinal Study of Incidence and Predictive Factors
Authors: Dierking Leah , Markides Kyriakos , Al Snih Soham , Kristen Peek M. 
Published: October 2016

ObjectivesTo determine predictors of fear of falling in older Mexican Americans over time.DesignLongitudinal study.SettingCommunity‐dwelling residents throughout California, Colorado, New Mexico, Arizona, and Texas.ParticipantsCommunity‐dwelling Mexican Americans aged 72 and older participating in the Hispanic Established Populations for the Epidemiologic Study of the Elderly from 2000–01 to 2010–11 (N = 1,682).MeasurementsFear of falling was measured at baseline and at each subsequent wave. Baseline demographic and clinical variables included social support, fall history, depression symptoms, Mini‐Mental State Examination (MMSE) score, activity of daily living (ADL) and instrumental ADL (IADL) limitations, and chronic health conditions.ResultsNine hundred fifty three (56.7%) subjects reported fear of falling at baseline, 262 of whom reported severe fear of falling. The predictors of reporting any fear of falling over time included female sex, frequent familial interaction, depression, chronic health conditions, IADL limitations, higher MMSE score, and three or more falls in the last 12 months. Predictors of severe fear of falling included older age, female sex, married, depressive symptoms, chronic health conditions, IADL limitations, higher MMSE score, and fall history. Protective factors included frequent friend interaction and higher levels of education.ConclusionFear of falling is prevalent in older Mexican‐American adults. The presence of friends nearby was shown to be protective against, whereas the presence of family nearby was shown to be predictive of fear of falling.
Shared Risk Factors for Constipation, Fecal Incontinence, and Combined Symptoms in Older U.S. Adults
Authors: Andy Uduak U. , Vaughan Camille P. , Burgio Kathryn L. , Alli Foluke M. , Goode Patricia S. , Markland Alayne D. 
Published: October 2016

ObjectivesTo estimate the prevalence of constipation, fecal incontinence (FI), and combined symptoms and to identify shared factors associated with bowel symptoms in older U.S. men and womenDesignPopulation‐based cross‐sectional study.SettingNational Health and Nutrition Examination Survey (2005–2010).ParticipantsWomen and men aged 50 and older.MeasurementsConstipation was defined as hard stool consistency on the validated Bristol Stool Form Scale or stool frequency of fewer than three bowel movements per week. FI was defined as at least monthly loss of solid, liquid, or mucus stool. Combined symptoms was defined as constipation and FI. Multinomial multivarible models adjusted for age, race, socioeconomic status, education, self‐rated health, depression, impairments in activities of daily living, and number of comorbidities.ResultsWomen (n = 3,078) reported higher prevalence of bowel symptoms than men (constipation 11.8% vs 4.7%%, FI 11.2% vs 8.6%, combined symptoms 1.4% vs 0.4%). In adjusted models, women had greater odds of having constipation (odds ratio (OR) = 3.0, 95% confidence interval (CI) = 2.3–3.8), FI (OR = 1.4, 95% CI = 1.1–1.8), and combined symptoms (OR = 4.6, 95% CI = 2.0–10.2) than men. Shared risk factors included poor self‐rated health and depression symptoms (constipation: OR = 1.8, 95% CI = 1.4–2.4 and OR = 1.8, 95% CI = 1.0–3.2; FI: OR = 1.6, 95% CI = 1.2–2.2 and OR = 2.3 95% CI = 1.4–3.6; combined symptoms: OR = 2.6 95% CI = 1.5–4.8 and OR = 4.6, 95% CI = 1.3–16.4).ConclusionWhen defining constipation and FI using validated instruments, women had a much higher prevalence of constipation than men, whereas men had a higher prevalence of FI than constipation. Shared risk factors reflect the negative effect that bowel symptoms have on quality of life.