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Article ; Online: Nanobody cytokine blockers in psoriasis.

Rubel, Diana

2021 Volume 397, Issue 10284, Page(s) 1523–1524

MeSH term(s)	Antibodies, Monoclonal ; Cytokines ; Humans ; Psoriasis/drug therapy
Chemical Substances	Antibodies, Monoclonal ; Cytokines
Language	English
Publishing date	2021-04-24
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(21)00873-4
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Article ; Online: Dogs in public spaces of Buenos Aires, Argentina: Exploring patterns of the abundance of dogs, the canine faecal contamination, the behaviour of people with dogs, and its relationships with demographic/economic variables.

Rubel, Diana / Carbajo, Aníbal

Preventive veterinary medicine

2019 Volume 170, Page(s) 104713

Abstract: The level of faecal contamination in urban public spaces depends on the behaviour of dogs's owners as well as on dog abundance. The aims of the present study were to explore patterns of the relative abundance of dogs, the canine faecal contamination, the ...

Abstract	The level of faecal contamination in urban public spaces depends on the behaviour of dogs's owners as well as on dog abundance. The aims of the present study were to explore patterns of the relative abundance of dogs, the canine faecal contamination, the behaviour of owners and dog walkers towards their pets, and their relationship with human demographic/economic variables in Buenos Aires city. We carried out a cross sectional study that included 67 randomly selected sampling sites (street corners). Each sampling site was evaluated one only time by two trained students under our supervision and all sighted dogs between 7 and 11 a.m. in both sidewalks of each corner were counted (spring 2013, 23 days of sampling). Data about dogs and people were obtained by using a standardized questionnaire and by direct observation. Feces censuses in 242 sidewalks were carried out. The sidewalks were randomly selected and its characteristics were registered (i.e. number of shops, trees). GIS was loaded with the city´s cartography and the values for nine variables used as demographic/economic indicators were obtained disaggregated by demographic units (National Census). Generalized linear models were used to identify the environmental and demographic variables related to the number of dogs sighted per site and feces per sidewalk. Explanatory variables per site included human density, number of inhabitants, households, precarious housing, proportion of children, maximum educational level and drinking water provision. For the sidewalks number of shops, trees, tree pits, broken sectors and total length were added. Also, variables regarding dog's owners and dog walkers behaviour were compared. A total of 1193 dog's owners, 234 dog walkers and 2835 dogs were sighted. The number of observed pets and that of people sighted with dogs showed a positive relationship with the economic level and the human density. The stool number per sidewalk increased with the higher number of broken sectors, higher number of tree pits per meter of sidewalk and the lower number of shops on it. The stool number per sidewalk was lower when 40% or more people with dogs carried waste bag to clean dogs' feces. Our results indicate that dog walkers compared to owners showed different behavioural patterns towards the pets (bag to remove dog's fouling, leash use, use of the green spaces, etc).
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Argentina ; Bonding, Human-Pet ; Cities ; Cross-Sectional Studies ; Dogs/physiology ; Feces ; Female ; Humans ; Male ; Middle Aged ; Population Density ; Socioeconomic Factors ; Young Adult
Language	English
Publishing date	2019-07-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	43399-8
ISSN	1873-1716 ; 0167-5877
ISSN (online)	1873-1716
ISSN	0167-5877
DOI	10.1016/j.prevetmed.2019.104713
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Article: Dogs in public spaces of Buenos Aires, Argentina: Exploring patterns of the abundance of dogs, the canine faecal contamination, the behaviour of people with dogs, and its relationships with demographic/economic variables

Rubel, Diana / Carbajo, Aníbal

Preventive veterinary medicine. 2019 Oct. 01, v. 170

2019

Abstract: The level of faecal contamination in urban public spaces depends on the behaviour of dogs’s owners as well as on dog abundance. The aims of the present study were to explore patterns of the relative abundance of dogs, the canine faecal contamination, the ...

Abstract	The level of faecal contamination in urban public spaces depends on the behaviour of dogs’s owners as well as on dog abundance. The aims of the present study were to explore patterns of the relative abundance of dogs, the canine faecal contamination, the behaviour of owners and dog walkers towards their pets, and their relationship with human demographic/economic variables in Buenos Aires city.We carried out a cross sectional study that included 67 randomly selected sampling sites (street corners). Each sampling site was evaluated one only time by two trained students under our supervision and all sighted dogs between 7 and 11 a.m. in both sidewalks of each corner were counted (spring 2013, 23 days of sampling). Data about dogs and people were obtained by using a standardized questionnaire and by direct observation. Feces censuses in 242 sidewalks were carried out. The sidewalks were randomly selected and its characteristics were registered (i.e. number of shops, trees). GIS was loaded with the city ́s cartography and the values for nine variables used as demographic/economic indicators were obtained disaggregated by demographic units (National Census). Generalized linear models were used to identify the environmental and demographic variables related to the number of dogs sighted per site and feces per sidewalk. Explanatory variables per site included human density, number of inhabitants, households, precarious housing, proportion of children, maximum educational level and drinking water provision. For the sidewalks number of shops, trees, tree pits, broken sectors and total length were added. Also, variables regarding dog’s owners and dog walkers behaviour were compared.A total of 1193 dog’s owners, 234 dog walkers and 2835 dogs were sighted. The number of observed pets and that of people sighted with dogs showed a positive relationship with the economic level and the human density.The stool number per sidewalk increased with the higher number of broken sectors, higher number of tree pits per meter of sidewalk and the lower number of shops on it. The stool number per sidewalk was lower when 40% or more people with dogs carried waste bag to clean dogs’ feces. Our results indicate that dog walkers compared to owners showed different behavioural patterns towards the pets (bag to remove dog’s fouling, leash use, use of the green spaces, etc).
Keywords	cartography ; censuses ; children ; cross-sectional studies ; defecation ; dogs ; drinking water ; economic indicators ; educational status ; feces ; geographic information systems ; green infrastructure ; households ; humans ; linear models ; pets ; questionnaires ; spring ; trees ; walking ; wastes ; Argentina
Language	English
Dates of publication	2019-1001
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	43399-8
ISSN	1873-1716 ; 0167-5877
ISSN (online)	1873-1716
ISSN	0167-5877
DOI	10.1016/j.prevetmed.2019.104713
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Article: Organoprotective Effects of Spironolactone on Top of Ramipril Therapy in a Mouse Model for Alport Syndrome.

Rubel, Diana / Zhang, Yanqin / Sowa, Nenja / Girgert, Rainer / Gross, Oliver

Journal of clinical medicine

2021 Volume 10, Issue 13

Abstract: Angiotensin-converting enzyme inhibitors (ACEi) delay progression of the inherited renal disease Alport syndrome. However, the effect of ACEis weakens gradually due to an "aldosterone escape". Here, we investigate if an aldosterone antagonist can ... ...

Abstract	Angiotensin-converting enzyme inhibitors (ACEi) delay progression of the inherited renal disease Alport syndrome. However, the effect of ACEis weakens gradually due to an "aldosterone escape". Here, we investigate if an aldosterone antagonist can counteract loss of ACEi-efficacy.
Language	English
Publishing date	2021-06-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10132958
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Article ; Online: Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome.

Zhang, Yanqin / Böckhaus, Jan / Wang, Fang / Wang, Suxia / Rubel, Diana / Gross, Oliver / Ding, Jie

Pediatric nephrology (Berlin, Germany)

2021 Volume 36, Issue 9, Page(s) 2719–2730

Abstract: Background: Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone ... ...

Abstract	Background: Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS. Methods: Retrospective study in 101 patients with ARAS from Chinese Registry Database of Hereditary Kidney Diseases and European Alport Registry. Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in ARAS were evaluated. Results: Median age was 15 years (range 1.5-46 years). Twelve patients progressed to stage 5 chronic kidney disease (CKD5) at median age 20.5 years. Patients without missense variants had both higher prevalence and earlier onset age of hearing loss, nephrotic-range proteinuria, more rapid decline of eGFR, and earlier onset age of CKD5 compared to patients with 1 or 2 missense variants. Most patients (79/101, 78%) currently are treated with RAAS inhibitors; median age at therapy initiation was 10 years and mean duration 6.5 ± 6.0 years. Median age at CKD5 for untreated patients was 24 years. RAAS inhibition therapy delayed CKD5 onset in those with impaired kidney function (T-III) to median age 35 years, but is undefined in treated patients with proteinuria (T-II) due to low number of events. No treated patients with microalbuminuria (T-I) progressed to CKD5. ARAS patients with 1 or 2 missense variants showed better response to treatment than patients with non-missense-variants. Conclusions: Our study provides the first evidence for early use of RAAS inhibition therapy in patients with ARAS. Furthermore, genotype in ARAS correlates with response to therapy in favor of missense variants.
MeSH term(s)	Adolescent ; Adult ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Child ; Child, Preschool ; Genotype ; Humans ; Infant ; Middle Aged ; Nephritis, Hereditary/drug therapy ; Nephritis, Hereditary/genetics ; Phenotype ; Protective Agents/therapeutic use ; Renin-Angiotensin System/drug effects ; Retrospective Studies ; Young Adult
Chemical Substances	Angiotensin-Converting Enzyme Inhibitors ; Protective Agents
Language	English
Publishing date	2021-03-27
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-021-05040-9
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Article: A luminal intermediate cell state maintains long-term prostate homeostasis and contributes to tumorigenesis.

Luo, Fu / Tshering, Lara F / Tutuska, Karis / Szenk, Mariola / Rubel, Diana / Rail, James G / Russ, Savanah / Liu, Jingxuan / Nemajerova, Alice / Balázsi, Gábor / Talos, Flaminia

bioRxiv : the preprint server for biology

2023

Abstract: Cellular heterogeneity poses tremendous challenges for developing cell-targeted therapies and biomarkers of clinically significant prostate cancer. The origins of this heterogeneity within normal adult and aging tissue remain unknown, leaving cellular ... ...

Abstract	Cellular heterogeneity poses tremendous challenges for developing cell-targeted therapies and biomarkers of clinically significant prostate cancer. The origins of this heterogeneity within normal adult and aging tissue remain unknown, leaving cellular states and transcriptional programs that allow expansions of malignant clones unidentified. To define cell states that contribute to early cancer development, we performed clonal analyses and single cell transcriptomics of normal prostate from genetically-engineered mouse models. We uncovered a luminal transcriptional state with a unique "basal-like" Wnt/p63 signaling (
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.24.529762
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Article ; Online: Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation.

Rhode, Heidrun / Lüse, Alexandra / Tautkus, Bärbel / Nabity, Mary / John-Kroegel, Ulrike / Weigel, Friederike / Dost, Axel / Schitke, Julia / Metzing, Oliver / Böckhaus, Jan / Rubel, Diana / Kiess, Wieland / Gross, Oliver

Kidney international reports

2023 Volume 8, Issue 12, Page(s) 2778–2793

Abstract: Introduction: Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage ... ...

Abstract	Introduction: Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to ensure preemptive therapy, early diagnosis is an essential prerequisite. Methods: To provide early diagnosis, we searched for protein biomarkers (BMs) by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate BMs. Of these, using commercial enzyme-linked immunosorbent assays (ELISAs), we evaluated 27 in dogs and 28 in children, 50 with AS and 104 healthy controls. Results: Most BMs from blood appeared as fractions of multiple variants of the same protein, as shown by their chromatographic distribution before mass spectrometry. Blood samples showed only minor differences because ELISAs rarely detect disease-specific variants. However, in urine , several proteins, individually or in combination, were promising indicators of very early and preclinical kidney injury. The BMs with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP). Conclusion: We generated very strong candidate BMs by our approach of first examining preclinical AS in dogs and then validating these BMs in children at early stages of disease. These BMs might serve for screening purposes for AS before the onset of kidney damage and therefore allow preemptive therapy.
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2023.09.028
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Article ; Online: A subset analysis of efficacy and safety outcomes from phase 3 clinical studies of ixekizumab for the treatment of patients with severe plaque psoriasis.

Spelman, Lynda / Rubel, Diana / Brnabic, Alan / Burkhardt, Nicole / Riedl, Elisabeth / Foley, Peter

The Journal of dermatological treatment

2020 Volume 33, Issue 1, Page(s) 329–335

Abstract: Background: Factors beyond the Psoriasis Area and Severity Index (PASI) contribute to disease severity in psoriasis and potentially affect treatment responses.: Objective: This subset analysis of data from two phase 3 clinical studies assessed ... ...

Abstract	Background: Factors beyond the Psoriasis Area and Severity Index (PASI) contribute to disease severity in psoriasis and potentially affect treatment responses. Objective: This subset analysis of data from two phase 3 clinical studies assessed baseline parameters in patients with different degrees of psoriasis severity in order to determine treatment responses to ixekizumab and safety outcomes. Methods: This study used integrated data from the UNCOVER-2 and -3 trials involving 2709 patients with chronic plaque psoriasis to assess the efficacy and safety of ixekizumab in three subgroups of patients, defined by PASI > 15 (group 1), PASI > 15 and history of ≥3 non-biologic systemic therapies (group 2), or PASI = 12-15 (group 3). Results: In groups 1 and 2, additional baseline features were identified that could influence treatment responses, including age at disease onset, Dermatology Life Quality Index, and work productivity. Irrespective of subgroup, ixekizumab demonstrated high PASI responses at weeks 12 and 60, which were evident as early as week 2. Adverse events did not differ across subgroups. Conclusion: Our data support the efficacy, early onset of action, and maintained response of ixekizumab as observed in previous trials, and highlight the complexity of comprehensively defining disease severity in psoriasis.
MeSH term(s)	Antibodies, Monoclonal, Humanized/adverse effects ; Dermatologic Agents/adverse effects ; Humans ; Psoriasis/drug therapy ; Severity of Illness Index ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal, Humanized ; Dermatologic Agents ; ixekizumab (BTY153760O)
Language	English
Publishing date	2020-04-21
Publishing country	England
Document type	Clinical Trial, Phase III ; Journal Article
ZDB-ID	1036299-x
ISSN	1471-1753 ; 0954-6634
ISSN (online)	1471-1753
ISSN	0954-6634
DOI	10.1080/09546634.2020.1752888
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Article ; Online: Immune mechanisms shape the clonal landscape during early progression of prostate cancer.

Tshering, Lara F / Luo, Fu / Russ, Savanah / Szenk, Mariola / Rubel, Diana / Tutuska, Karis / Rail, James G / Balázsi, Gábor / Shen, Michael M / Talos, Flaminia

Developmental cell

2023 Volume 58, Issue 12, Page(s) 1071–1086.e8

Abstract: Understanding the role of the immune microenvironment in modulating intratumor heterogeneity is essential for effective cancer therapies. Using multicolor lineage tracing in genetically engineered mouse models and single-cell transcriptomics, we show ... ...

Abstract	Understanding the role of the immune microenvironment in modulating intratumor heterogeneity is essential for effective cancer therapies. Using multicolor lineage tracing in genetically engineered mouse models and single-cell transcriptomics, we show that slowly progressing tumors contain a multiclonal landscape of relatively homogeneous subpopulations within a well-organized tumor microenvironment. In more advanced and aggressive tumors, however, the multiclonal landscape develops into competing dominant and minor clones accompanied by a disordered microenvironment. We demonstrate that this dominant/minor landscape is associated with differential immunoediting, in which minor clones are marked by an increased expression of IFNγ-response genes and the T cell-activating chemokines Cxcl9 and Cxcl11. Furthermore, immunomodulation of the IFNγ pathway can rescue minor clones from elimination. Notably, the immune-specific gene signature of minor clones exhibits a prognostic value for biochemical recurrence-free survival in human prostate cancer. These findings suggest new immunotherapy approaches for modulating clonal fitness and tumor progression in prostate cancer.
MeSH term(s)	Male ; Animals ; Mice ; Humans ; Prostatic Neoplasms/genetics ; Chemokines ; Interferon-gamma ; Clone Cells ; Tumor Microenvironment
Chemical Substances	Chemokines ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2023.04.010
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Article: Systematic Review and Meta-Analysis of Inflammatory Bowel Disease Adverse Events with Anti-Interleukin 17A Agents and Tumor Necrosis Factor Inhibitors in Rheumatic Disease and Skin Psoriasis.

Truong, Steven L / Chin, Jasmine / Liew, David F L / Zahir, Syeda Farah / Ryan, Elizabeth G / Rubel, Diana / Radford-Smith, Graham / Robinson, Philip C

Rheumatology and therapy

2021 Volume 8, Issue 4, Page(s) 1603–1616

Abstract: Introduction: The aim of this work is to perform a systematic review and meta-analysis of anti-tumor necrosis factor (anti-TNF) and anti-interleukin-17 (anti-IL-17) trials for spondyloarthritis, psoriatic arthritis, and psoriasis comparing rates of ... ...

Abstract	Introduction: The aim of this work is to perform a systematic review and meta-analysis of anti-tumor necrosis factor (anti-TNF) and anti-interleukin-17 (anti-IL-17) trials for spondyloarthritis, psoriatic arthritis, and psoriasis comparing rates of inflammatory bowel disease (IBD) events compared to placebo. Methods: MEDLINE, EMBASE, and The Cochrane Library were searched for double-blind, randomized placebo-controlled anti-TNF and anti-IL-17 trials of included diseases. Inflammatory bowel disease events from the RCT period were pooled and meta-analyzed using statistical methods suitable for low-event-rate meta-analysis (Peto's, Mantel-Haenszel, hypergeometric-normal model, and Shuster-Guo-Skyler). When observed data were insufficient, we performed an exploratory sensitivity analysis to compare methods. Results: We identified 9551 original papers, and included 96 publications: 65 anti-TNF and 31 anti-IL-17 trials, containing 21 new and 12 flare IBD events in 28,209 participants. New IBD on anti-IL-17 occurred 0.23/100 patient-years (PY) in psoriasis, 0.61/100 PY in PsA and 1.63/100 PY in spondyloarthritis, rates similar to observational cohorts, and less commonly on anti-TNF (0/100 PY, 0/100 PY, 0.32/100 PY, respectively). No evidence of difference between groups was found, with wide CI from many pooled counts of zero, especially in placebo arms. Conclusions: IBD events were rare, occurring at rates similar to biologic-naive groups. We could not find statistically significant differences in risk of new or recurrent IBD between treatment and control groups using selected meta-analytical methods for low event rate scenarios. Meta-analyses of this topic require more IBD events, ideally without pooling heterogeneous groups. Larger, thoroughly reported trials with systematic and detailed safety reporting are required to improve risk estimation and to make accurate inferences.
Language	English
Publishing date	2021-08-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2783278-8
ISSN	2198-6584 ; 2198-6576
ISSN (online)	2198-6584
ISSN	2198-6576
DOI	10.1007/s40744-021-00360-6
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