bluuebunny/crossref_metadata_2025_split huggingface dataset:
What exactly distinguishes aggressive from chronic periodontitis: is it mainly a difference in the degree of bacterial invasiveness?
Authors: Van der Velden Ubele 
Published: July 2017

AbstractAt the International Workshop for Classification of Periodontal Diseases and Conditions in 1999, the classification of aggressive and chronic periodontitis that is presently used was introduced. A literature review of papers published in 2015 and having aggressive periodontitis in the title revealed that most studies use this terminology but it is questionable whether all established criteria were really applied correctly. Review of the literature showed no qualitative differences between aggressive and chronic periodontitis regarding bacterial and viral aspects. It is also unlikely that that there are major immunologic differences between aggressive and chronic periodontitis. Neutrophil function can be compromised in both conditions but may be more genetically related in aggressive periodontitis and be associated more with lifestyle factors in chronic periodontitis. In general, genetics plays a more important role in aggressive periodontitis than in chronic periodontitis. It is likely that periodontitis progresses by recurrent acute episodes during which invasion of bacteria into the connective tissue may occur. Two cases are presented for which invasive periodontitis is treated with systemic antibiotics, showing remarkable periodontal healing in terms of probing attachment gain, as well as radiographic bone gain. Periodontitis in an active state with bacterial invasion is probably accompanied with a significant increase in subgingival temperature. It is hypothesized that elevated subgingival temperature may help to distinguish between invasive and non‐invasive periodontitis. Scaling and root planing during a burst of disease activity may result in removal of connective tissue fiber attachment and down‐growth of epithelium, thereby preventing the reattachment of connective tissue. Because the burst of disease is accompanied by an increase of temperature, assessment of the temperature may help in deciding whether or not to prescribe systemic antibiotics. When the use of systemic antibiotics is indicated, the antibiotic therapy may help to maintain the connective tissue attachment at the most possible coronal level. The above implies that the ability to diagnose bacterial invasive periodontitis is quite important, and future research is needed to determine if assessment of subgingival temperature may help in diagnosing invasive periodontitis. In addition, it is suggested that future classification systems of periodontitis include the item of bacterial invasive periodontitis.
The periodontal war: microbes and immunity
Authors: Ebersole Jeffrey L. , Dawson Dolph , Emecen‐Huja Pinar , Nagarajan Radhakrishnan , Howard Katherine , Grady Martha E. , Thompson Katherine , Peyyala Rebecca , Al‐Attar Ahmad , Lethbridge Kathryn , Kirakodu Sreenatha , Gonzalez Octavio A. 
Published: July 2017

AbstractMaintenance of periodontal health or transition to a periodontal lesion reflects the continuous and ongoing battle between the vast microbial ecology in the oral cavity and the array of resident and emigrating inflammatory/immune cells in the periodontium. This war clearly signifies many ‘battlefronts’ representing the interface of the mucosal‐surface cells with the dynamic biofilms composed of commensal and potential pathogenic species, as well as more recent knowledge demonstrating active invasion of cells and tissues of the periodontium leading to skirmishes in connective tissue, the locality of bone and even in the local vasculature. Research in the discipline has uncovered a concerted effort of the microbiome, using an array of survival strategies, to interact with other bacteria and host cells. These strategies aid in colonization by ‘ambushing, infiltrating and outflanking’ host cells and molecules, responding to local environmental changes (including booby traps for host biomolecules), communicating within and between genera and species that provideMASINT(Measurement and Signature Intelligence) to enhance sustained survival, sabotage the host inflammatory and immune responses and by potentially adopting a ‘Fabian strategy’ with a war of attrition and resulting disease manifestations. Additionally, much has been learned regarding the ever‐increasing complexity of the host‐response armamentarium at both cellular and molecular levels that is addressed in this review. Knowledge regarding how these systems fully interact requires both new laboratory and clinical tools, as well as sophisticated modeling of the networks that help maintain homeostasis and are dysregulated in disease. Finally, the triggers resulting in a ‘coup de main’ by the microbiome (exacerbation of disease) and the characteristics of susceptible hosts that can result in ‘pyrrhic victories’ with collateral damage to host tissues, the hallmark of periodontitis, remains unclear. While much has been learned, substantial gaps in our understanding of the ‘parameters of this war’ remain elusive toward fulfilling the Sun Tzu adage: ‘If you know the enemy and know yourself, you need not fear the result of a hundred battles.’
OptimalA PrioriBalance in the Design of Controlled Experiments
Authors: Kallus Nathan 
Published: July 2017

SummaryWe develop a unified theory of designs for controlled experiments that balance baseline covariates a priori (before treatment and before randomization) using the framework of minimax variance and a new method called kernel allocation. We show that any notion of a priori balance must go hand in hand with a notion of structure, since with no structure on the dependence of outcomes on baseline covariates complete randomization (no special covariate balance) is always minimax optimal. Restricting the structure of dependence, either parametrically or non-parametrically, gives rise to certain covariate imbalance metrics and optimal designs. This recovers many popular imbalance metrics and designs previously developed ad hoc, including randomized block designs, pairwise-matched allocation and rerandomization. We develop a new design method called kernel allocation based on the optimal design when structure is expressed by using kernels, which can be parametric or non-parametric. Relying on modern optimization methods, kernel allocation, which ensures nearly perfect covariate balance without biasing estimates under model misspecification, offers sizable advantages in precision and power as demonstrated in a range of real and synthetic examples. We provide strong theoretical guarantees on variance, consistency and rates of convergence and develop special algorithms for design and hypothesis testing.
Kinematic stride cycle asymmetry is not associated with sprint performance and injury prevalence in athletic sprinters
Authors: Haugen T. , Danielsen J. , McGhie D. , Sandbakk Ø. , Ettema G. 
Published: July 2017

The aims of this study were to (a) quantify the magnitude of kinematic stride cycle asymmetry in high‐level athletic sprinters, (b) explore the association between kinematic asymmetry and maximal sprint running performance, and (c) investigate possible associations between kinematic asymmetry and injury prevalence. Twenty‐two competitive sprinters (age 23 ± 3 year, height 1.81 ± 0.06 m, body mass 75.5 ± 5.6 kg, personal best 100 m 10.86 ± 0.22 seconds) performed 2‐3 flying sprints over 20 m. Kinematics were recorded in 3D using a motion tracking system with 21 cameras at a 250 Hz sampling rate, allowing assessment of six consecutive steps for each athlete. Information about injuries sustained 1 year prior to and after the experiment was continuously registered (type, location, severity/duration, and time of year occurrence). The results showed that ≥11 of the 22 participating athletes displayed large or very large asymmetry for at least 11 of 14 variables, and all athletes displayed large or very large asymmetry for at least three variables. No correlations between individual magnitudes of asymmetry and sprint performance were significant (trivial to moderate). No significant changes in asymmetry between best and worst trial were observed for any of the analyzed variables. In addition, injured and non‐injured athletes did not differ in asymmetry, neither for the time period 1 year prior to nor after the test. In conclusion, kinematic asymmetries in the stride cycle were not associated with neither maximal sprint running performance nor the prevalence of injury among high‐level athletic sprinters.
The identification of nutrient limitations on eutrophication in Dianchi Lake, China
Authors: Liu Xujun 
Published: July 2017

AbstractDue to rapid urbanisation and economic development, Dianchi Lake has been eutrophic since the 1980s. Control of nutrient loading is regarded as the primary restoration method. Two independent approaches: analysis of 13 years of Dianchi Lake monitoring data using Support Vector Machines (SVM) and a nutrient‐enrichment experiment, identified phosphorus and nitrogen as simultaneously limiting. Total phosphorus (TP) has a clear, stable correlation with chlorophyll‐a (Chl‐a) concentrations in Dianchi Lake. Compared to total nitrogen (TN), TP shows a stronger correlation when Chl‐a concentration is below 0.051 mg/L and an almost equal correlation when it is above this level. An excessive phosphorus to nitrogen ratio may stimulate compensatory fixation of atmospheric N2 by cyanobacteria; therefore, only reducing the external nitrogen input may not necessarily result in lower total nitrogen and chlorophyll concentrations. We recommend that reducing the lake TP load to the lowest economically‐feasible level is the most cost‐effective restoration measure.
Reviewer Acknowledgements
Authors: Young James 
Published: July 2017

International Journal of Social Science Studies (IJSSS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether IJSSS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 5, Number 8 Agboola O. Paul, Universiti Teknologi Malaysia, MalaysiaAhmet Yıkmış, Abant Izzet Baysal Univeersity, TurkeyAmanda ElBassiouny, Spring Hill College, USABegoña Montero-Fleta, Universitat Politécnica de València, SpainBo Li, St Ambrose University, USABonnie L McIntyre, Catholic University of America, Washington D.C., USAE.Ozan Aksoz, Anadolu University, TurkeyEmanuele Achino, C. D. T. O., ItalyGhazali Bello Abubakar, Sokoto State University, NigeriaGülsüm Depeli, Hacettepe University, TurkeyHenry Poduthas, West Texas A&M University, USAJadranka Svarc, Institute of Social Sciences Ivo Pilar, Zagreb, CroatiaJehu Onyekwere Nnaji, University of Naples II,Italy and Globe Visions Network Italy, ItalyJulia M. Mack, Gannon University, USAK.O. Aramide, The Polytechnic Ibadan, NigeriaKatja Eman, Univerza v Mariboru, SloveniaLaura Diaconu Maxim, "Alexandru Ioan Cuza University" of Iasi, RomaniaMickey Langlais, University of Nebraska – Kearney, USAMohammad Naji Shah Mohammadi, Kuala Lumpur, MalaysiaPriyono, Economics Faculty Universities, IndonesiaQingzhi Huan, Peking University, ChinaRasa Poceviciene, Siauliai University, LithuaniaShariq aziz butt, Superior University Lahore, PakistanValentina Evangelista, G. d’Annunzio University, ItalyYaghoob Foroutan , The University of Waikato, New ZealandYanzhe Zhang, Jilin University, China, China/AustraliaZafer İbrahimoglu, Marmara University, Turkey
Abstract 1114: Combining anti-androgen therapy and PARP inhibition results in synergistic cytotoxicity of metastatic castration-resistant prostate cancer (mCRPC) cells
Authors: Pamarthy Sahithi , Sagar Vinay , Vatapalli Rajita J. , Reinstein Zachary , Ansari Muhammad Zayd , Filho Benedito A. Carneiro , Giles Francis J. , Abdulkadir Sarki A. 
Published: July 2017

Abstract
Androgen deprivation therapy is an efficient first line therapy for advanced prostate cancer. However, in most cases resistance inevitably develops resulting in metastatic castration-resistant prostate cancer (mCRPC). Abiraterone and enzalutamide are approved to treat mCRPC and act by inhibiting androgen biosynthesis and androgen receptor (AR) signaling, respectively. Poly (ADP-ribose) polymerase 1 (PARP1) is a key enzyme in the DNA damage repair pathway and has also been implicated in AR signaling cascade. Recent reports suggest significant efficacy combining anti-androgens and inhibitors of Poly (ADP-ribose) polymerase (PARP) particularly against cells harboring mutations in the DNA repair pathway. Here, we provide evidence of synergistic cytotoxicity combining PARP inhibition and androgen signaling ablation in the AR positive human CRPC cell line 22RV1 harboring mutation in the DNA repair gene BRCA2. The PARP inhibitor talazoparib (IC50 - 0.05 μM) was upto 20 times more potent than olaparib (IC50 – 1.0 μM) in inducing cell death in 22RV1 as seen by cell viability and clonogenic assays. When combined with AR antagonist enzalutamide (IC50 – 0.25 μM) or androgen synthesis inhibitor abiraterone (IC50 – 1.25 μM) both PARP inhibitors showed significant synergy, although talazoparib was more prominent owing to its superior potency. Higher concentrations of enzalutamide and abiraterone (&gt;10μM) induced PARP cleavage and increased expression of γ-H2AX, a marker for DNA damage. Our results suggest that AR signaling inhibition involves PARP mediated apoptosis and highlight the crosstalk between PARP and AR pathways. In summary, combining anti-androgen therapy and PARP inhibitors carry significant therapeutic potential for CRPC patients harboring mutations in DNA repair pathway.
Citation Format: Sahithi Pamarthy, Vinay Sagar, Rajita J. Vatapalli, Zachary Reinstein, Muhammad Zayd Ansari, Benedito A. Carneiro Filho, Francis J. Giles, Sarki A. Abdulkadir. Combining anti-androgen therapy and PARP inhibition results in synergistic cytotoxicity of metastatic castration-resistant prostate cancer (mCRPC) cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1114. doi:10.1158/1538-7445.AM2017-1114
Abstract 1125: Eukaryotic Elongation Factor 2 Kinase (eEF-2K) is a novel therapeutic target in BRCA1+ mutated breast cancer
Authors: Asik Elif , Kahraman Nermin , Guray Tulin , Volkan Murvet , Lopez-Berestein Gabriel , Ozpolat Bulent 
Published: July 2017

Abstract
BReast CAncer 1 and 2 (BRCA1/2) tumor suppressor genes are frequently mutated in familial breast and ovarian cancers. Recent clinical trials in breast cancers with BRCA1/2 mutations indicate that 50-75% of patients may not have response to poly (ADP-ribose) polymerase inhibitors (PARP) inhibitors. Thus, identification of novel molecular targets and therapeutic interventions are needed to improve poor clical outcome and patient survival. Here we report that Eukaryotic Elongation Factor-2 Kinase (EF2K), an atypical kinase, is highly upregulated in BRCA1+ mutated cell lines and involved in colony formation, migration/ invasion and enhances the effect of PARP inhibitors. Furthermore, in vivo therapeutic targeting of EF2K by once a week systemic injections with magnetic nanoparticles (MNPs) incorporating EF2K siRNA significantly inhibits growth of BRCA1+ tumors in orthotopic xenograft models in mice by inhibition of tumor cell proliferation, angiogenesis and induction of robust apoptosis, which were associated with in vivo inhibition of clinically relevant molecular pathways including, proliferation, survival/drug resistance (PI3K/Akt, c-Myc), cell cycle (Cyclin D1), motility/invasion (Src/FAK/Paxillin), translation (4E-BP1), angiogenesis (VEGF) and stem-cell markers. No toxicity was detected during the study and by postmortem analysis of major organs, indicating that targeting EF2K is safe. The combination of PARP inhibitor (AZD2281, Oleparib) with MNP-EF2K siRNA enhanced significantly growth inhibition in MDA-MB-436 cells indicting EF2K siRNA sensitize BRCA1 + mutation breast cancer cells to PARP inhibitors. Collectively, our results suggest, for the first time, that EF2K is involved in tumorigenesis and progression and may serve as a potential therapeutic target in BRCA1+ mutated breast cancers.
Citation Format: Elif Asik, Nermin Kahraman, Tulin Guray, Murvet Volkan, Gabriel Lopez-Berestein, Bulent Ozpolat. Eukaryotic Elongation Factor 2 Kinase (eEF-2K) is a novel therapeutic target in BRCA1+ mutated breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1125. doi:10.1158/1538-7445.AM2017-1125
Abstract 1168: Efficacy of the IRAK4 inhibitor CA-4948 in patient-derived xenograft models of diffuse large B cell lymphoma
Authors: Booher Robert N. , Samson Maria Elena , Xu Guang-Xin , Cheng Hongsheng , Tuck David P. 
Published: July 2017

Abstract
IRAK4 kinase activity is required for toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling in a variety of myeloid and lymphoid cell types. Recruitment of IRAK4 to these receptors and its subsequent activation is facilitated by the MYD88 adaptor protein, which is mutated in ~22% of DLBCL cases. The MYD88 L265P activating mutation is found in ~30% of the activated B-cell (ABC) and ~6% of germinal center B-cell (GCB) subtypes of DLBCL and leads to constitutive activation of NF-κB signaling that is associated with worse prognosis. Thus, the development of small molecule inhibitors targeting IRAK4 is an attractive anticancer strategy for MYD88 mutation-containing cancers such as DLBCL.
We are developing an IRAK4 inhibitor, CA-4948, as a therapeutic agent for hematological cancers with dysregulated TLR/MYD88/IRAK4 signaling. CA-4948 (previously AU-4948) is a selective and potent IRAK4 kinase inhibitor with in vivo activity in a TLR4-induced cytokine release model. CA-4948 exhibits favorable DMPK properties, oral bioavailability, and is well tolerated in mice. Furthermore, CA-4948 was previously shown to exhibit dose-dependent efficacy in ABC-DLBCL MYD88-L265P xenograft tumor models using cell lines OCI-LY3 and OCI-LY10.
Here, we report the efficacy results from testing CA-4948 in a panel of well characterized, patient-derived DLBCL tumor xenograft (PDX) mouse models. CA-4948 exhibited the greatest efficacy in four of the five ABC-DLBCL PDX models tested as compared to GBC-DLBCL and ABC/GCB DLBCL PDX models. Furthermore, CA-4948 was efficacious in ABC-DLBCL PDX tumors containing activating mutations in both TLR/IL-1R and BCR signaling pathways (MYD88 and CD79B double mutants). Interestingly, the one ABC-DLBCL PDX model that failed to respond to CA-4948 treatment contained a MYD88 L265P mutation as well as a BCL6 translocation. While this particular PDX model was resistant to CA-4948, and showed a weak anti-tumor response to single-agent ibrutinib, the combination treatment of ibrutinib and CA-4948 exhibited a synergistic tumor growth inhibition effect. In summary, CA-4948 exhibited anti-tumor activity in ABC-type DLCBL PDX tumor models including those containing combinations of activating mutations in the TLR/IL-1R and BCR signaling pathways. These results underscore the therapeutic potential of IRAK4 kinase inhibition by CA-4948, as a single-agent or in combination with BCR inhibitors, for the treatment of DLBCL.
Citation Format: Robert N. Booher, Maria Elena Samson, Guang-Xin Xu, Hongsheng Cheng, David P. Tuck. Efficacy of the IRAK4 inhibitor CA-4948 in patient-derived xenograft models of diffuse large B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1168. doi:10.1158/1538-7445.AM2017-1168
Abstract 1188: Sodium phenylbutyrate has an antineoplastic effect and enhances the cytotoxicity of 5-fluorouracil and irinotecan in colorectal cancer cell lines
Authors: Al-Keilani Maha , Darweesh Ruba 
Published: July 2017

Abstract
Colorectal cancer is the third most common cancer in the world and it is the second leading cause of cancer-related deaths in the United States. About 25% of colorectal cancer cases present with metastases at time of diagnosis and 50% of patients who undergo surgery will ultimately develop metastatic disease. Consequently, adjuvant chemotherapy is required in many cases and it aims to prevent tumor progression and metastasis.
Resistance to chemotherapy is the biggest obstacle in the treatment path of advanced colorectal cancer. Thus, highlighting the urgent need for the identification of new therapeutic agents that can enhance the cytotoxicity of the currently approved anticancer drugs.
Sodium phenylbutyrate (NaPB), a salt of a short chain fatty acid that is used for treatment of urea cycle disorders, is under investigation for its antineoplastic potential. NaPB acts as a histone deacetylase inhibitor and it has been shown to be associated with reduced ER stress and enhanced JNK signaling pathway. This indicates that NaPB may enhance the cytotoxicity of the currently approved agents for colorectal cancer including oxaliplatin, 5-fluorouracil, and irinotecan.
The aims of this study were to identify the antineoplastic potential of NaPB in colorectal cell lines, and to identify its effect on the cytotoxicity of oxaliplatin, 5-fluorouracil, and irinotecan.
MTT proliferation assay showed that NaPB possessed a concentration dependent killing effect against HCT-116 and HT-29 colorectal cancer cell line (IC50 values were 5 and 10 mM respectively). Moreover, at clinically achievable and nontoxic concentration (2.5 mM), NaPB showed a synergistic effect in HCT-116 on 5-fluorouracil (R=14.176, p=0.006), on irinotecan (R=53.86, p=0.0117), and on oxaliplatin (R=20, p=0.004), but resulted in extensive cytotoxicity when used at 5 mM and 10 mM.
In HT-29 cells, NaPB at concentrations 5 mM and 10 mM, showed a synergistic effect on 5-fluorouracil (R=5.5, p&lt;0.001; and R=125, p&lt;0.001 respectively), on irinotecan (R=5.7, p=0.016; and R=21.3, p=0.018 respectively), and on oxaliplatin (R=2.4, p=0.003; and R=3, p=0.002 respectively). The addition of NaPB at concentration of 20 mM to the previous drugs resulted in profound cytotoxic effect toward HT-29 cells.
As a conclusion, NaPB is a promising new adjuvant antineoplastic agent that can be used to enhance the cytotoxicity of 5-fluorouracil, irinotecan, and oxaliplatin in colorectal cancer.
Citation Format: Maha Al-Keilani, Ruba Darweesh. Sodium phenylbutyrate has an antineoplastic effect and enhances the cytotoxicity of 5-fluorouracil and irinotecan in colorectal cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1188. doi:10.1158/1538-7445.AM2017-1188