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  1. Article ; Online: Discovery of ( R)-8-(6-Methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4- b]pyrrol-2-yl)-3-(1-methylcyclopropyl)-2-((1-methylcyclopropyl)amino)quinazolin-4(3 H)-one, a Potent and Selective Pim-1/2 Kinase Inhibitor for Hematological Malignancies.

    Wang, Hui-Ling / Andrews, Kristin L / Booker, Shon K / Canon, Jude / Cee, Victor J / Chavez, Frank / Chen, Yuping / Eastwood, Heather / Guerrero, Nadia / Herberich, Brad / Hickman, Dean / Lanman, Brian A / Laszlo, Jimmy / Lee, Matthew R / Lipford, J Russell / Mattson, Bethany / Mohr, Christopher / Nguyen, Yen / Norman, Mark H /
    Pettus, Liping H / Powers, David / Reed, Anthony B / Rex, Karen / Sastri, Christine / Tamayo, Nuria / Wang, Paul / Winston, Jeffrey T / Wu, Bin / Wu, Qiong / Wu, Tian / Wurz, Ryan P / Xu, Yang / Zhou, Yihong / Tasker, Andrew S

    Journal of medicinal chemistry

    2019  Volume 62, Issue 3, Page(s) 1523–1540

    Abstract: Pim kinases are a family of constitutively active serine/threonine kinases that are partially redundant and regulate multiple pathways important for cell growth and survival. In human disease, high expression of the three Pim isoforms has been implicated ...

    Abstract Pim kinases are a family of constitutively active serine/threonine kinases that are partially redundant and regulate multiple pathways important for cell growth and survival. In human disease, high expression of the three Pim isoforms has been implicated in the progression of hematopoietic and solid tumor cancers, which suggests that Pim kinase inhibitors could provide patients with therapeutic benefit. Herein, we describe the structure-guided optimization of a series of quinazolinone-pyrrolodihydropyrrolone analogs leading to the identification of potent pan-Pim inhibitor 28 with improved potency, solubility, and drug-like properties. Compound 28 demonstrated on-target Pim activity in an in vivo pharmacodynamic assay with significant inhibition of BAD phosphorylation in KMS-12-BM multiple myeloma tumors for 16 h postdose. In a 2-week mouse xenograft model, daily dosing of compound 28 resulted in 33% tumor regression at 100 mg/kg.
    MeSH term(s) Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Female ; Hematologic Neoplasms/drug therapy ; Humans ; Mice, SCID ; Molecular Structure ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/pharmacokinetics ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors ; Pyrroles/chemical synthesis ; Pyrroles/pharmacokinetics ; Pyrroles/therapeutic use ; Quinazolinones/chemical synthesis ; Quinazolinones/pharmacokinetics ; Quinazolinones/therapeutic use ; Structure-Activity Relationship ; Swine ; Xenograft Model Antitumor Assays
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors ; Pyrroles ; Quinazolinones ; Proto-Oncogene Proteins c-pim-1 (EC 2.7.11.1)
    Language English
    Publishing date 2019-01-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.8b01733
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reply to Gopa Iyer, Bernard H. Bochner, Eliezer M. Van Allen, David B. Solit, and Jonathan E. Rosenberg's Letter to the Editor re: Russell E.N. Becker, Alexa R. Meyer, Aaron Brant, et al. Clinical Restaging and Tumor Sequencing are Inaccurate Indicators of Response to Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.07.016.

    Becker, Russell E N / Baras, Alex / Bivalacqua, Trinity J

    European urology

    2020  Volume 79, Issue 2, Page(s) e58–e59

    MeSH term(s) Humans ; Male ; Muscles ; Neoadjuvant Therapy ; Prostatic Neoplasms ; Urinary Bladder Neoplasms
    Language English
    Publishing date 2020-11-17
    Publishing country Switzerland
    Document type Letter ; Comment
    ZDB-ID 193790-x
    ISSN 1873-7560 ; 1421-993X ; 0302-2838
    ISSN (online) 1873-7560 ; 1421-993X
    ISSN 0302-2838
    DOI 10.1016/j.eururo.2020.11.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Benzene-Centered Tri- and Tetrametallacarborane Sandwich Complexes Organotransition-Metal Metallacarboranes, part 56. This work was supported in part by the National Science Foundation (grant CHE 9980708 to R.N.G.) and the Deutsche Forschungsgemeinschaft (SFB 247, to W.S. for M.B.). Part 55: T. Dodge, M. A. Curtis, J. M. Russell, M. Sabat, M. G. Finn, R. N. Grimes, J. Am. Chem. Soc. 2000, 122, 10 573.

    Bluhm, Martin / Pritzkow, Hans / Siebert, Walter / Grimes, Russell N.

    Angewandte Chemie (International ed. in English)

    2000  Volume 39, Issue 24, Page(s) 4562–4564

    Language English
    Publishing date 2000-12-15
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: nido<-->closo Interconversion of Six-Vertex Metallacarboranes: Access to CoC(2)B(3) and CoC(2)B(4) Clusters with Nonadjacent Carbon Atoms Organotransition-Metal Metallacarboranes, part 57. This work was supported in part by the National Science Foundation (grant CHE 9980708) and the Alexander von Humboldt Foundation (Feodor Lynen postdoctoral fellowship to H.-J. Schanz). Part 56: M. Bluhm, H. Pritzkow, W. Siebert, R. N. Grimes, Angew. Chem. 2000, 112, 4736; Angew. Chem. Int. Ed. 2000, 39, 4562.

    Schanz, Hans-Jörg / Sabat, Michal / Grimes, Russell N.

    Angewandte Chemie (International ed. in English)

    2001  Volume 40, Issue 14, Page(s) 2705–2707

    Language English
    Publishing date 2001-07-16
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Biased agonists of GPR84 and insights into biological control.

    Luscombe, Vincent B / Wang, Pinqi / Russell, Angela J / Greaves, David R

    British journal of pharmacology

    2024  Volume 181, Issue 10, Page(s) 1509–1523

    Abstract: GPR84 was first identified as an open reading frame encoding an orphan Class A G protein coupled receptor in 2001. Gpr84 mRNA is expressed in a limited number of cell types with the highest levels of expression being in innate immune cells, M1 polarised ... ...

    Abstract GPR84 was first identified as an open reading frame encoding an orphan Class A G protein coupled receptor in 2001. Gpr84 mRNA is expressed in a limited number of cell types with the highest levels of expression being in innate immune cells, M1 polarised macrophages and neutrophils. The first reported ligands for this receptor were medium chain fatty acids with chain lengths between 9 and 12 carbons. Subsequently, a series of synthetic agonists that signal via the GPR84 receptor were identified. Radioligand binding assays and molecular modelling with site-directed mutagenesis suggest the presence of three ligand binding sites on the receptor, but the physiological agonist(s) of the receptor remain unidentified. Here, we review the effects of GPR84 agonists on innate immune cells following a series of chemical discoveries since 2001. The development of highly biased agonists has helped to probe receptor function in vitro, and the remaining challenge is to follow the effects of biased signalling to the physiological functions of innate immune cell types. LINKED ARTICLES: This article is part of a themed issue GPR84 Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.10/issuetoc.
    MeSH term(s) Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Macrophages ; Ligands ; Phagocytosis
    Chemical Substances Receptors, G-Protein-Coupled ; Ligands
    Language English
    Publishing date 2024-01-23
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.16310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Aboriginal and Torres Strait Islander youth suicide mortality and previous mental health, suicidality and service use in Queensland, Australia, from 2001 to 2021.

    Gibson, M / Leske, S / Ward, R / Weir, B / Russell, K / Kolves, K

    Journal of affective disorders

    2024  Volume 354, Page(s) 55–61

    Abstract: Background: The current study aimed to compare current suicide rates, trends, previous treatment, suicidality and mental health diagnoses for First Nations and non-Indigenous young people who died by suicide.: Methods: Age-specific suicide rates ( ... ...

    Abstract Background: The current study aimed to compare current suicide rates, trends, previous treatment, suicidality and mental health diagnoses for First Nations and non-Indigenous young people who died by suicide.
    Methods: Age-specific suicide rates (ASSRs) were calculated per 100,000 persons/year using suicides aged 10-19 years in the Queensland Suicide Register. Rate Ratios (RRs) and 95 % CIs compared ASSRs for First Nations and non-Indigenous youth dying by suicide in Queensland, Australia, from 2001 to 2018. Risk ratios (RiskR) with 95 % CIs compared characteristics between First Nations and non-Indigenous youth suicides. Joinpoint regression was used to identify any changes in trends and annual percentage change (APC) in suicides with 95 % CIs.
    Results: The First Nations youth ASSR was 24.71 deaths per 100,000 persons/year, 4.5 times the non-Indigenous ASSR (95 % CI = 3.74-5.38, p < 0.001). Both non-Indigenous and First Nations suicide trends were stable with no joinpoints (APC: 0.3 %, 95 % CI: -1.6-2.2, p = 0.78; APC: 0.9 %, 95 % CI: -0.2-2.1, p = 0.11). Less than a quarter (23.9 %) of First Nations young people had ever received mental health treatment, significantly fewer than non-Indigenous youth (RiskR = 0.80, 95 % CI = 0.71-0.90, p < 0.001). Similarly, in the three months preceding their death, only 14.5 % of First Nations young people had received mental health treatment (RiskR = 0.89, 95 % CI = 0.83-97, p = 0.015).
    Limitations: Reported mental illness, suicidality and help-seeking could be underreported due to concealment from family or police.
    Conclusions: The current study finds no change in the gap between the First Nations and Non-Indigenous youth suicide rates nor evidence of decrease in the First Nations youth suicide rate. There is a need for alternative approaches to Indigenous youth suicide prevention, such as assertive outreach models outside of traditional triage and mental health systems to proactively build trusting relationships with young people in communities to identify young people needing support.
    MeSH term(s) Humans ; Adolescent ; Queensland/epidemiology ; Suicide/psychology ; Mental Health ; Australian Aboriginal and Torres Strait Islander Peoples ; Australia
    Language English
    Publishing date 2024-03-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 135449-8
    ISSN 1573-2517 ; 0165-0327
    ISSN (online) 1573-2517
    ISSN 0165-0327
    DOI 10.1016/j.jad.2024.03.013
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  7. Article: The Stigma of Epilepsy among Patients Attending the Epilepsy Clinic at Connaught Hospital, Sierra Leone.

    Lisk, Durodami R / Kanu, Alieu / Russell, James B W

    West African journal of medicine

    2023  Volume 40, Issue 11, Page(s) 1209–1215

    Abstract: Background: Epilepsy is one of the world's most common neurological disorders with about eighty percent of cases living in low and middle-income countries. Due to superstitious cultural and traditional beliefs in Sub-Saharan Africa, the stigma ... ...

    Abstract Background: Epilepsy is one of the world's most common neurological disorders with about eighty percent of cases living in low and middle-income countries. Due to superstitious cultural and traditional beliefs in Sub-Saharan Africa, the stigma associated with epilepsy is particularly disabling. Stigma negatively affects the psychosocial wellbeing of people with epilepsy (PWE) and their acceptance of medical treatment. Very limited studies have been done on the types and extent of stigma in PWE in Sierra Leone.
    Objective: This study will assess the extent and correlates of perceived and enacted stigma among patients attending the epilepsy clinic at Connaught hospital in Freetown, Sierra Leone.
    Methods: Using a semi-structured questionnaire to identify both perceived and enacted stigma, a cross-sectional descriptive study was conducted among patients attending the epilepsy clinic at Connaught hospital aged ten years and above with no major psychiatric co-morbidity. Frequency of stigma and socio-demographic and clinical correlates of stigma were determined.
    Results: Of the 128 patients, (9 below 18 years) 57.8% were males. Participants had a mean age of 32.9 years. 53.9% and 79.9% of participants reported experiencing perceived and enacted stigma, respectively. Longer duration of illness and being single correlated with perceived stigma, while lower educational achievement and early age of onset of seizure correlated with enacted stigma. A seizure frequency of more than two attacks a month was significantly related to both forms of stigma.
    Conclusion: The level of epilepsy-related social stigma is high in Sierra Leone. This is likely due to poor community education, leading to misconceptions and biases. An appropriate educational intervention coupled with effective clinical management of cases is needed to mitigate epilepsy-related stigma.
    Contexte: L'épilepsie est l'un des troubles neurologiques les plus courants dans le monde, avec environ quatre-vingts pour cent des cas vivant dans des pays à revenu faible et intermédiaire. En raison des croyances culturelles et traditionnelles superstitieuses en Afrique subsaharienne, la stigmatisation associée à l'épilepsie est particulièrement handicapante. La stigmatisation affecte négativement le bien-être psychosocial des personnes épileptiques (PWE) et leur acceptation du traitement médical. Très peu d'études ont été menées sur les types et l'étendue de la stigmatisation chez les PWE en Sierra Leone.
    Objectif: Cette étude évaluera l'étendue et les corrélats de la stigmatisation perçue et manifeste chez les patients fréquentant la clinique de l'épilepsie à l'hôpital Connaught à Freetown, Sierra Leone.
    Méthodes: À l'aide d'un questionnaire semi-structuré pour identifier la stigmatisation perçue et manifeste, une étude descriptive transversale a été menée chez des patients fréquentant la clinique de l'épilepsie à l'hôpital Connaught, âgés de dix ans et plus, sans co-morbidité psychiatrique majeure. La fréquence de la stigmatisation et les corrélats socio-démographiques et cliniques de la stigmatisation ont été déterminés.
    Résultats: Sur les 128 patients (9 de moins de 18 ans), 57,8% étaient des hommes. Les participants avaient un âge moyen de 32,9 ans. 53,9% et 79,9% des participants ont signalé avoir éprouvé une stigmatisation perçue et manifeste, respectivement. Une durée plus longue de la maladie et le fait d'être célibataire étaient corrélés à la stigmatisation perçue, tandis qu'un niveau d'éducation inférieur et un jeune âge de début des crises étaient corrélés à la stigmatisation manifeste. Une fréquence de crises de plus de deux attaques par mois était significativement liée aux deux formes de stigmatisation.
    Conclusion: Le niveau de stigmatisation sociale liée à l'épilepsie est élevé en Sierra Leone. Cela est probablement dû à une éducation communautaire insuffisante, conduisant à des idées fausses et des préjugés.Une intervention éducative appropriée couplée à une gestion clinique efficace des cas est nécessaire pour atténuer la stigmatisation liée à l'épilepsie.
    Mots-clés: Épilepsie, Manifeste, Perçue, Stigmatisation, Sierra Leone.
    MeSH term(s) Male ; Humans ; Adult ; Female ; Sierra Leone/epidemiology ; Social Stigma ; Cross-Sectional Studies ; Epilepsy ; Seizures
    Language English
    Publishing date 2023-12-14
    Publishing country Nigeria
    Document type Journal Article
    ZDB-ID 1132088-6
    ISSN 0189-160X
    ISSN 0189-160X
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  8. Article ; Conference proceedings: Time spent for handling gastroscopes and colonoscopes in the operating theatre: A prospective observational study

    Nielsen, K. / Miliam, P. B. / Adamsen, S. / Russell, R. V.

    Endoscopy

    2024  Volume 56, Issue S 02

    Event/congress ESGE Days 2024, Berlin, Germany, 2024-04-25
    Language English
    Publishing date 2024-04-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 80120-3
    ISSN 1438-8812 ; 0013-726X
    ISSN (online) 1438-8812
    ISSN 0013-726X
    DOI 10.1055/s-0044-1783798
    Database Thieme publisher's database

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  9. Article ; Online: Outcome measures for young people with adolescent idiopathic scoliosis: A qualitative exploration of healthcare professionals' perceptions and practices.

    Alamrani, Samia / Gardner, Adrian / Falla, Deborah / Russell, Emily / Rushton, Alison B / Heneghan, Nicola R

    PloS one

    2024  Volume 19, Issue 1, Page(s) e0297339

    Abstract: Background: Limited knowledge exists on current use of patient reported outcome measures (PROMs) and performance measures for adolescents with idiopathic scoliosis (AIS), as well as health care professionals' (HCPs) perceived barriers and facilitators ... ...

    Abstract Background: Limited knowledge exists on current use of patient reported outcome measures (PROMs) and performance measures for adolescents with idiopathic scoliosis (AIS), as well as health care professionals' (HCPs) perceived barriers and facilitators towards their use. This study's objectives were: 1) to explore current practice of HCPs when assessing outcomes for AIS 2) to understand perceived barriers and facilitators of HCPs to use PROMs 3) to understand perceived barriers and facilitators of HCPs to use performance measures.
    Methods: A qualitative study recruited a purposive sample of HCPs from a tertiary hospital in the United Kingdom. Mean years of experience managing individuals with AIS was 11.8 years; and included surgeons, physiotherapists and nurses, educated at Bachelor, Masters and Doctoral level. Consent to participate and demographic information were collected in advance of the interviews. In-depth, virtual semi-structured interviews were informed by a topic guide based on current evidence. Interviews of approximately 45 minutes were audio and video recorded and transcribed verbatim alongside written field notes. Data were coded and analysed using inductive thematic analysis, involving researchers with topic and methodological expertise and input from a patient representative.
    Results: Two themes emerged regarding current practice of using PROMs routine practice and personal evaluations. Four themes emerged as barriers to using PROMs for individuals with AIS: priority and support (e.g., HCPs focus on providing care), practical challenges (e.g., inadequate PROMs), patient-related challenges (e.g., patient preferences) and knowledge, education, and perceived value. Two themes emerged as facilitators: quality existing measure (e.g., sufficient psychometric properties), and priority and support (e.g., research department/culture). Themes for barriers to use performance measures were practicality (e.g., need physical space) and perceived value and knowledge (e.g., PROMs are more important), while the one theme for facilitators was practical consideration (e.g., acceptability).
    Conclusions: Although HCPs perceived the value of using outcome measures, current practice indicates limited use for individuals with AIS. The findings revealed different barriers and facilitators to implement PROMs in practice. Adopting performance measure are limited due to lack of knowledge and perceived value alongside the practicality, while considering practical factors can improve the use of these measures in practice.
    MeSH term(s) Humans ; Adolescent ; Scoliosis/therapy ; Health Personnel/education ; Qualitative Research ; Delivery of Health Care ; Outcome Assessment, Health Care
    Language English
    Publishing date 2024-01-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0297339
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Randomized Pilot Study of a Keratin-based Topical Cream for Radiation Dermatitis in Breast Cancer Patients.

    Winkfield, Karen M / Hughes, Ryan T / Brown, Doris R / Clohessy, Ryan M / Holder, Robert C / Russell, Gregory B / Rejeski, Alexis F / Burnett, Luke R

    Technology in cancer research & treatment

    2024  Volume 23, Page(s) 15330338231222137

    Abstract: Purpose: ...

    Abstract Purpose:
    MeSH term(s) Humans ; Female ; Keratins ; Pilot Projects ; Breast Neoplasms/complications ; Breast Neoplasms/radiotherapy ; Quality of Life ; Radiodermatitis/etiology
    Chemical Substances Keratins (68238-35-7)
    Language English
    Publishing date 2024-01-07
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2146365-7
    ISSN 1533-0338 ; 1533-0346
    ISSN (online) 1533-0338
    ISSN 1533-0346
    DOI 10.1177/15330338231222137
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