bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of periodontal therapy in management of common complex systemic diseases and conditions: An update
Authors: Sabharwal Amarpreet , Gomes‐Filho Isaac S. , Stellrecht Elizabeth , Scannapieco Frank A. 
Published: September 2018

AbstractThe goal of this review is to summarize the results of randomized trials reported since 2010 that assessed the effect of periodontal interventions on at least one systemic outcome in human subjects of any age, gender or ethnicity. Oral outcome measures included gingivitis, pocket depth, clinical attachment loss and/or radiographic bone loss and oral hygiene indices. Studies were excluded if the trial was not completed or if treatment was not randomized. The results suggest that nonsurgical periodontal intervention provided to pregnant women is safe and improves periodontal status without preventing adverse pregnancy outcomes. Nonsurgical periodontal intervention was also found to provide modest improvement in glycemic control in individuals with type 2 diabetes mellitus and periodontitis. Also, improving oral care through mechanical or chemical control of dental‐plaque biofilm formation can contribute to the prevention of respiratory infections in differing clinical settings, including hospitals and nursing homes, and in patients with chronic obstructive pulmonary disease. No clinical trials were reported that tested the effect of periodontal interventions on medical outcomes of atherosclerosis, cardiovascular diseases, stroke, rheumatoid arthritis, Alzheimer's disease, chronic kidney disease or malignant neoplasia.
Stress, allostatic load, and periodontal diseases
Authors: Sabbah Wael , Gomaa Noha , Gireesh Aswathikutty 
Published: September 2018

AbstractPsychosocial stress plays an important role in periodontal disease through biological and behavioral pathways. In this paper we review studies that examine the relationship between stress and periodontal diseases, and discuss the different measures used to assess stress. Self‐reported measures, such as the Perceived Stress Scale and the Stress Appraisal Measure, have traditionally been used to assess stress. Frequent and repeated exposure to stressor(s) leads to wear and tear of the body's systems, resulting in what is known as allostatic load. In recent years, few studies examining the relationship between stress and periodontal diseases have used an aggregate variable, including primary and secondary markers of allostatic load, as a biological marker of stress. While research on the relationship between allostatic load and periodontal disease is still developing, as most of the studies used cross‐sectional data, this line of research presents a good opportunity for establishing a composite biological indicator as a risk factor for periodontal disease. Such an indicator is also potentially beneficial for personalized periodontics as it will help to target intervention to specific levels of risk and will help in integrating oral and general health promotion policies.
The impact of infection among left ventricular assist device recipients on post‐transplantation outcomes: A retrospective review
Authors: Lerman Dana T. , Hamilton Keith W. , Byrne Dana , Lee Doreen F. , Zeitler Kristen , Claridge Tamara , Gray Jaime , Minamoto Grace Y. 
Published: September 2018

AbstractIntroductionLeft ventricular assist device (LVAD) infections are common, and the consequences of LVAD infections on orthotopic heart transplantation (OHT) outcomes are not well described.AimsThe aim of this study was to describe clinical characteristics and evaluate risk factors for developing LVAD infections, and examine outcomes of LVAD‐specific infections (VSI) after OHT.MethodsWe retrospectively investigated the records of 74 consecutive patients at two institutions who had undergone LVAD placement and subsequent OHT between January 2007 and December 2012.ResultsForty‐six of 74 (62%) LVAD recipients who underwent OHT had pre‐transplant infections, and 18 (24%) had LVAD‐specific infection (VSI), of which 71% were caused by gram‐negative organisms. Of pre‐transplant non‐LVAD infections, Clostridium difficile infection (CDI) was the most common (26%) followed by urinary tract infection (UTI, 16%) and pneumonia (PNA 15%). Univariate analysis comparing subjects with VSI to those without VSI showed a significant association with time spent outside the hospital prior to transplantation (median 231.8 days vs 142.2 days, P < 0.03) and total time between VAD placement and OHT (244.0 days and 150.5 days, P < 0.002). Logistic regression was performed and significant predictors for VAD‐related infection were age and the presence of diabetes, with type of device as an effect modifier. Six months post‐OHT survival was not significantly affected by the presence of VSI prior to transplant. There was a trend toward an association between the presence of any infection and post‐transplant rejection (P < 0.09). There were 10 post‐transplant deaths by 6 months. Of these deaths, 4/10 (40%) were cardiopulmonary and 6/10 (60%) were related to infections.ConclusionsAdvanced age and presence of diabetes were predictors of VSI, as well as type of VAD device, although device choice is likely affected by many clinical factors including age and comorbidities, as well as institution‐specific preferences. VSI was not associated with a decrease in 6‐month post‐OHT survival. However, infections remain the major causes of death by 6 months post‐transplant. Certain infections are associated with an increased risk of rejection, which merits further investigation.
GBGT1 is allelically diverse but dispensable in humans and naturally occurring anti‐FORS1 shows an ABO‐restricted pattern
Authors: Hult Annika K. , McSherry Eoin , Möller Mattias , Olsson Martin L. 
Published: September 2018

BACKGROUNDThe FORS histo‐blood group system was described in 2013 and much remains to be investigated regarding its genetic and immunohematologic characteristics, as well as its clinical importance. While presence of the c.887G>A‐mutated GBGT1 gene, which results in FORS1 glycosphingolipid expression on human red blood cells (RBCs), is rare in the populations tested so far, naturally occurring anti‐FORS1 in plasma appears common.STUDY DESIGN AND METHODSThe Erythrogene database was utilized to probe genetic variation in GBGT1 among 2504 individuals in the 1000 Genomes Project. We screened 1108 Swedish blood donors for three principally important single‐nucleotide polymorphisms (c.363C>A, c.886C>T, and c.887G>A) and selected samples were analyzed further. Screening for naturally occurring anti‐FORS1 in plasma from 100 donors was performed using antigen‐positive RBCs.RESULTSWe identified 68 GBGT1 alleles, of which three were previously listed blood group alleles. Eight potential null alleles were observed, based on three different nonsense mutations. Four healthy donors were found homozygous for c.363C>A, which truncates the GBGT1‐encoded Fs synthase prematurely. This is the first description of human knock‐outs for GBGT1. The c.886C>T mutation that alters the same codon (p.Arg296Trp) changed by c.887G>A (p.Arg296Gln) was overexpressed to investigate if it induces the FORS1+ phenotype. However, c.886C>T did not result in synthesis of FORS1. We detected anti‐FORS1 in 10% of all donors tested but none in the A1 or A1B groups.CONCLUSIONWe have extended the knowledge of GBGT1 variants, allele frequencies, and the characteristics of naturally occurring antibodies in our newest carbohydrate blood group system, FORS. The finding of c.363C>A‐homozygous donors indicates that GBGT1 is dispensable.
Analytical validation of platelet microparticle quantification in cats
Authors: Cremer Signe E. , Koch Jørgen , Graversen Nanna , Gravgaard Anne S. , Langhorn Rebecca , Kristensen Annemarie T. , Willesen Jakob L. , Nielsen Lise N. 
Published: September 2018

BackgroundCardiogenic embolism (CE) in cats is a devastating condition primarily associated with hypertrophic cardiomyopathy (HCM). Hypercoagulability may pose a risk for thrombus formation; however, no single test can predictCEdevelopment. Platelet microparticles (PMPs) released from platelet membranes are associated with thrombosis in humans.ObjectivesThe aims were to validate flow cytometricPMPquantification in cats analytically and, in a pilot study, evaluate the procoagulant annexin V (AnV) positivePMPconcentration in healthy cats and cats with asymptomaticHCM.MethodsWithCD61 as a platelet marker,CD61+AnV+PMPs (0.3‐1.0 μm) were quantified in citrated whole blood (WB) and platelet‐poor plasma (PPP) using flow cytometry. Analyses were performed in 6 healthy cats and 5 cats with asymptomaticHCM. The coefficient of variation (CV) for duplicate (intra‐assay) and parallel (inter‐assay) analyses were calculated.ResultsPMPconcentrations were quantified with acceptable intra‐assayCVforWB(CD61+/AnV‐; 2.4%, 0.2%‐8.4% (median, range),CD61+/AnV+; 3.8%, 0.1%‐12.5%) andPPP(CD61+/AnV‐; 5.0%, 0.7%‐12.8%,CD61+/AnV+; 7.4%, 0.5%‐15.3%), and acceptable inter‐assayCVforWBin 10/11 cats (CD61+/AnV‐; 6.2%, 1.4%‐13.3%,CD61+/AnV+; 6.4%, 0.7%‐17.2%), but unacceptable forPPP(CD61+/AnV‐; 15.6%, 5.8%‐42.7%,CD61+/AnV+; 27.8%, 8.4%‐77.1%). ForWB PMPconcentrations, the pilot data demonstrated no differences between healthy cats and cats with asymptomaticHCM(4/5 with left ventricular outflow obstruction) for either theCD61+/AnV‐or theCD61+/AnV+PMPs.ConclusionsOnlyWB PMPconcentrations could be quantified reliably in cats in a clinical setting.PMPconcentrations did not differ between healthy and asymptomaticHCMcats in this pilot study.
Photocatalytic degradation of rhodamine B based on membrane catalyst of H3O40PW12/quaternized chitosan
Authors: Wan Heting , Wang Yifu , Wang Lulu , Wang Jilin , Feng Ruijiang 
Published: September 2018

AbstractIncreasing environmental pollution caused by toxic dyes due to their hazardous nature is a matter of great concern, and lacks the effective methods to remove them. Therefore, in this research a series of H3O40PW12/Quaternized chitosan (PWX%/QCS) membrane catalyst is synthesized based on QCS (positively charged) and keggin‐type H3O40PW12 (negatively charged), which is available to degrade rhodamine B. The optimum experimental conditions are investigated and results reveal that the degradation rate is over 92.1% and the chemical oxygen demand (COD) decreases is 78.09%, which is obtained based on the follow conditions is that the UV radiation is 90 min, the dose of membrane catalyst is 0.1g, the doping amount PW12 (H3O40PW12) is 35 wt%, RB aqueous solution (30mL) is 5mg/L, the reaction temperature is 30°C, pH = 5 and H2O2 is 20mM. The simulation result reveals that the photocatalytic degradation reaction of RB with PWX%/QCS membrane catalyst in an aqueous solution can be described by the Langmuir–Hinshelwood equation. And the initiation rate constant and the initiation adsorption constant in this case are 4.082mg/(L/min) and 0.01090L/mg, respectively.
Bokeloh bat lyssavirus isolation in a Natterer’s bat, Poland
Authors: Smreczak Marcin , Orłowska Anna , Marzec Anna , Trębas Paweł , Müller Thomas , Freuling Conrad M. , Żmudziński Jan F. 
Published: September 2018

AbstractIn recent years, Bokeloh bat lyssavirus (BBLV), a member of the novel lyssavirus genus Bokeloh bat lyssavirus in the family Rhabdoviridae, has been detected in Germany (five cases) and France (two cases). Here, we report the isolation of BBLV in a Natterer's bat (Myotis nattereri) in Poland. The bat brain tested positive for rabies using classical diagnostics tests (FAT and RTCIT) and then subsequently confirmed by molecular techniques. Viral RNA was found in all peripheral organs tested, and the highest viral loads were detected in brain, the salivary gland and bladder. Phylogenetic analysis performed on complete viral genome sequences revealed the closest homology to representatives of BBLV lineage B, isolated previously in southern Germany. This case provides further evidence that BBLV is widespread in Europe.
Overexpression or Deletion of Ergosterol Biosynthesis Genes Alters Doubling Time, Response to Stress Agents, and Drug Susceptibility in
Saccharomyces cerevisiae
Authors: Bhattacharya Somanon , Esquivel Brooke D. , White Theodore C. 
Published: September 2018

ABSTRACT

Ergosterol (ERG) is a critical sterol in the cell membranes of fungi, and its biosynthesis is tightly regulated by 25 known enzymes along the ERG production pathway. The effects of changes in expression of each ERG biosynthesis enzyme in
Saccharomyces cerevisiae
were analyzed by the use of gene deletion or plasmid-borne overexpression constructs. The strains overexpressing the ERG pathway genes were examined for changes in doubling time and responses to a variety of stress agents. In addition, ERG gene overexpression strains and ERG gene deletion strains were tested for alterations in antifungal drug susceptibility. The data show that disruptions in ergosterol biosynthesis regulation can affect a diverse set of cellular processes and can cause numerous phenotypic effects. Some of the phenotypes observed include dramatic increases in doubling times, respiratory deficiencies on glycerol media, cell wall insufficiencies on Congo red media, and disrupted ion homeostasis under iron or calcium starvation conditions. Overexpression or deletion of specific enzymes in the ERG pathway causes altered susceptibilities to a variety of classes of antifungal ergosterol inhibitors, including fluconazole, fenpropimorph, lovastatin, nystatin, amphotericin B, and terbinafine. This analysis of the effect of perturbations to the ERG pathway caused by systematic overexpression of each of the ERG pathway genes contributes significantly to the understanding of the ergosterol biosynthetic pathway and its relationship to stress response and basic biological processes. The data indicate that precise regulation of ERG genes is essential for cellular homeostasis and identify several ERG genes that could be exploited in future antifungal development efforts.

IMPORTANCE
A common target of antifungal drug treatment is the fungal ergosterol biosynthesis pathway. This report helps to identify ergosterol biosynthesis enzymes that have not previously been appreciated as drug targets. The effects of overexpression of each of the 25 ERG genes in
S. cerevisiae
were analyzed in the presence of six stress agents that target essential cellular processes (cell wall biosynthesis, protein translation, respiration, osmotic/ionic stress, and iron and calcium homeostasis), as well as six antifungal inhibitors that target ergosterol biosynthesis. The importance of identifying cell perturbations caused by gene overexpression or deletion is emphasized by the prevalence of gene expression alterations in many pathogenic and drug-resistant clinical isolates. Genes whose altered expression causes the most extensive phenotypic alterations in the presence of stressors or inhibitors have the potential to be drug targets.
Incidence and risk of major heart diseases in middle-aged adults with moderate to severe vision impairment: a population-based cohort study
Authors: Hsueh Chun-Mei , Wey Jing-Hwa , Yeh Jong-Shiuan , Wu Chien-Hua , Liou Tsan-Hon , Chang Kwang-Hwa 
Published: September 2018

Background/aimTo estimate the incidence and risk of major adverse cardiovascular events (MACEs), including heart failure and ischaemic heart disease, among middle-aged people with a visual disability (VD).MethodsWe used a national health insurance research database to conduct a population-based cohort study from 1 January 2000 to 31 December 2013. Patients with VD aged 35~65 years were recruited. For each VD patient, five age-matched, sex-matched and comorbidity-matched patients were randomly selected and recruited as controls. Control patients had no documented disability.ResultsThis study recruited 978 patients with VD (mean age±SD, 55.1±7.8 years; 48.9% male) and 4677 controls. Compared with the same sex of the controls, women with VD had higher incidence of MACE 1 (7.9 vs 2.8/1000 person-years, p<0.001), MACE 2 (27.5 vs 16.9/1000 person-years, p<0.001), MACE 3 (3.7 vs 1.4/1000 person-years, p<0.005) and MACE 4 (4.5 vs 2.5/1000 person-years, p<0.05), and men with VD had higher incidence of MACE 1 (4.6 vs 2.0/1000 person-years, p<0.005). Compared with the controls, patients with VD had lower cumulative MACE 1~MACE 4-free probabilities and had an independently higher risk of MACE 1~MACE 4 during the 13-year study, yielding an adjusted hazard ratio range of 1.31~2.75. Those persons with VD who had diabetes and hypertension had greater risks of MACE 1~MACE 4.ConclusionsMiddle-aged adults with VD were at risk of MACEs. A programme for MACE prevention is important for middle-aged people with VD. This is especially true for women and for those who also have diabetes and hypertension.
Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis
Authors: Shen Xian , Zhao Bin 
Published: September 2018

Abstract

Objective
To evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and PD-L1 negative.

Design
Meta-analysis of randomised controlled trials.

Data sources
PubMed, Embase, Cochrane database, and conference abstracts presented at the American Society of Clinical Oncology and European Society of Medical Oncology up to March 2018.

Review methods
Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab) that had available hazard ratios for death based on PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or tumour and immune cells, assayed by immunohistochemistry staining methods.

Results
4174 patients with advanced or metastatic cancers from eight randomised controlled trials were included in this study. Compared with conventional agents, PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66, 95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to 0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02 for interaction). Additionally, in both patients that were PD-L1 positive and PD-L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were observed consistently across interventional agent, cancer histotype, method of randomisation stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time.

Conclusions
PD-1 or PD-L1 blockade therapy is a preferable treatment option over conventional therapy for both patients that are PD-L1 positive and PD-L1 negative. This finding suggests that PD-L1 expression status alone is insufficient in determining which patients should be offered PD-1 or PD-L1 blockade therapy.
Discovery and Therapeutic Exploitation of Mechanisms of Resistance to MET Inhibitors in Glioblastoma
Authors: Cruickshanks Nichola , Zhang Ying , Hine Sarah , Gibert Myron , Yuan Fang , Oxford Madison , Grello Cassandra , Pahuski Mary , Dube Collin , Guessous Fadila , Wang Baomin , Deveau Ciana , Saoud Karim , Gallagher Isela , Wulfkuhle Julia , Schiff David , Phan See , Petricoin Emanuel , Abounader Roger 
Published: September 2018

Abstract

Purpose:
Glioblastoma (GBM) is the most common and most lethal primary malignant brain tumor. The receptor tyrosine kinase MET is frequently upregulated or overactivated in GBM. Although clinically applicable MET inhibitors have been developed, resistance to single modality anti-MET drugs frequently occurs, rendering these agents ineffective. We aimed to determine the mechanisms of MET inhibitor resistance in GBM and use the acquired information to develop novel therapeutic approaches to overcome resistance.
Experimental Design: We investigated two clinically applicable MET inhibitors: crizotinib, an ATP-competitive small molecule inhibitor of MET, and onartuzumab, a monovalent monoclonal antibody that binds to the extracellular domain of the MET receptor. We developed new MET inhibitor–resistant cells lines and animal models and used reverse phase protein arrays (RPPA) and functional assays to uncover the compensatory pathways in MET inhibitor–resistant GBM.

Results:
We identified critical proteins that were altered in MET inhibitor–resistant GBM including mTOR, FGFR1, EGFR, STAT3, and COX-2. Simultaneous inhibition of MET and one of these upregulated proteins led to increased cell death and inhibition of cell proliferation in resistant cells compared with either agent alone. In addition, in vivo treatment of mice bearing MET-resistant orthotopic xenografts with COX-2 or FGFR pharmacological inhibitors in combination with MET inhibitor restored sensitivity to MET inhibition and significantly inhibited tumor growth.

Conclusions:
These data uncover the molecular basis of adaptive resistance to MET inhibitors and identify new FDA-approved multidrug therapeutic combinations that can overcome resistance.
Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study
Authors: Yamaguchi Yoshitaka , Koga Masatoshi , Sato Shoichiro , Yamagami Hiroshi , Todo Kenichi , Okuda Satoshi , Okada Yasushi , Kimura Kazumi , Shiokawa Yoshiaki , Kamiyama Kenji , Itabashi Ryo , Hasegawa Yasuhiro , Kario Kazuomi , Fujita Kyohei , Kumamoto Masaya , Kamimura Teppei , Ando Daisuke , Ide Toshihiro , Yoshimoto Takeshi , Shiozawa Masayuki , Matsubara Soichiro , Yoshimura Sohei , Nagatsuka Kazuyuki , Toyoda Kazunori ,   for the SAMURAI Study Investigators
Published: September 2018

<b><i>Background:</i></b> Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. <b><i>Methods:</i></b> The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to &#x3c; 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became &#x3c; 160 mm Hg. <b><i>Results:</i></b> Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (<i>p</i> = 0.043 and <i>p</i> = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP &#x3c; 160 mm Hg between groups (<i>p</i> = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (<i>p </i>trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (&#x3c; 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038–0.867; <i>p</i> = 0.032). <b><i>Conclusions:</i></b> Early achievement of target SBP &#x3c; 160 mm Hg is associated with a lower risk of hematoma growth in ICH.