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1.
  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Moore, Amy, et al. (författare)
  • Genetically Determined Height and Risk of Non-hodgkin Lymphoma
  • 2020
  • Ingår i: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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  • Fornaro, M., et al. (författare)
  • MULTIMORBIDITY AND PROMIS HEALTH OUTCOMES IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES : DATA FROM A LARGE, GLOBAL E-SURVEY (COVAD STUDY)
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 942-943
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Prevalence of comorbidities and their impact on health outcomes in Idiopathic inflammatory myopathies (IIMs) is limited.Objectives: This study aimed to explore the prevalence of multimorbidity in patients with IIMs, other autoimmune rheumatic diseases (AIRDs) and Healthy controls (HCs). We further explore the impact of comorbidities on patients’ physical, mental, and social health assessed by the Patient-Reported Outcome Measurement Information System (PROMIS instruments).Methods: Data for this study were acquired from the COVAD 2 e-survey hosted by a study group consisting of 167 collaborators in 110 countries. Basic multimorbidity (BM) was defined as the co-occurrence of two or more comorbidities in an individual, while complex multimorbidity (CM) signified the co-occurrence of 3 or more chronic conditions affecting 3 or more different organ systems. PROMIS global physical health (PGP), mental health (PGM), fatigue 4a (F4a) and physical function short form (SF10) were analysed using descriptive statistics and linear regression models. Hierarchical Clustering on Principal Components was performed to outline the grouping.Results: Of 10740 complete respondents, 1558 IIMs, 4591 AIRDs and 3652 HCs were analysed. Individuals with IIMs exhibited high burden of any comorbidity (OR: 1.62 vs AIRDs and 2.95 vs HCs,p<0.01), BM (OR 1.66 vs AIRDs and 3.52 vs HCs,p<0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs,p<0.01), and mental health disorders (MHDs) (OR 1.33 vs AIRDs and 2.63 vs HCs,p<0.01).IIM patients with comorbidities (and MHDs) had worse physical function (low PGP, PGM, SF10 and higher F4a scores, all p<0.001). Worse physical function (PGP) was predicted by age (0.35; 0.030), active disease (-1.51; <0.001), BM (-1.11; <0.001), and MHDs (-1.47; <0.001). PGM was impacted by age (0.51; 0.004), active disease (-1.34, <0.001), BM (-0.75; 0.001) and MHDs (-2.22; <0.001). Determinants of SF10a were age (-3.86; <0.001), active disease (-7.03, <0.001), female (2.85, <0.001), BM (-2.95; <0.001) and MHDs (-2.37; <0.001). Fatigue (F4a) was impacted by age (-0.96, <0.001), active disease (1.45, <0.001), country human development index (0.95; 0.036), BM (1.11; <0.001); and MHDs (2.17; <0.001).Four distinct clusters (Figure 1A, Table 1) were identified i.e., cluster 0: lower burden of comorbidities and good health status; cluster 1: older patients, whit higher burden of comorbidities and poor health status, cluster 2: patients with higher prevalence of MHDs, lower PGP and PGM; and higher F4a scores; and lastly Cluster 3 that comprised older patients with an average burden of comorbidities and overall good health status according to PROMIS scores.Dermatomyositis, anti-synthetase syndrome, necrotizing autoimmune myopathy were similarly represented in all clusters, whilst inclusion body myositis and polymyositis were more predominant in clusters 1 (40.6% and 17.2%) and 3 (32 % and 17.5%), while overlap myositis was more represented in cluster 2 (25.6%) and 0 (32.7%) (Figure 1B).Conclusion: Patients with IIMs have a higher burden of comorbidities that adversely impact physical and mental health, calling for optimized approaches for holistic patient management.
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  • Gupta, L., et al. (författare)
  • COMORBIDITIES, COMPLEX MULTIMORBIDITY AND PROMIS HEALTH OUTCOMES AMONGAUTOIMMUNE RHEUMATIC DISEASES : DATA FROM THE COVAD STUDY
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 555-556
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Comorbidities have a profound impact on the QoL of patients living with autoimmune rheumatic diseases (AIRDs). Unfortunately, global data on the burden of comorbidities and its impact on health outcomes in this vulnerable group is scarce.Objectives: We studied the prevalence, distribution and clustering of comorbidities and multimorbidity among patients with AIRDs and healthy controls (HCs) and its impact on health outcomes, utilizing data from the ongoing 2nd COVAD study.Methods: The COVAD study is a global e-survey that embodies patient voice while empowering collaborators and young researchers. The study group of 157 physicians across 106 countries from February-June 2022 captured details of AIRDs, autoimmune and non-autoimmune comorbidities, and validated patient reported outcomes. Human Development Index (UNDP 2021-22) of country of residence was taken as a surrogate marker for socioeconomic status (SES).Basic multimorbidity (BM), Complex multimorbidity (CM), Autoimmune multimorbidity (AM) are defined as the co-occurrence of ≥2 non-rheumatic comorbidities, ≥3 non-rheumatic chronic conditions affecting ≥3 different organ systems [1] and ≥3 autoimmune diseases (AIDs) in an individual respectively.PROMIS global physical health (PGP), mental health (PGM), fatigue 4a (F4a) and physical function short form (SF10) scores were calculated for the different groups and compared using descriptive statistics, linear regression and cluster analysis (hierarchical followed by K means).Results: Of 17,612 total respondents, 6149 (62.7%) had underlying AIRDs and 3652 (37.3%) were HCs, with female (80.8%) and Caucasian (53.9%) predominance in the former.All types of multimorbidity were more frequent in AIRDs than HCs, including any comorbidity (77.1% versus 25.0%; OR: 2.9; 2.7-3.2), BM (21.0% vs 6.2%; 4.0; 3.4-4.6), and CM (3.1% vs 0.5%; 6.4; 3.9-10.4), and with prevalence increasing with age (p<0.001) (Figure 1A, B). Comorbidity prevalence was the highest among Americans and Australians (72% each).Patients with AIRDs had poorer health outcomes than HCs, including lower PGP, PGM, SF10, F4a scores (all p<0.001). Among AIRDs, those with comorbidities had lower physical function and PROMIS scores (PGP, PGM, and SF10), and reported fatigue more often (all p<0.001).Female gender, and underlying BM and AM particularly predisposed patients to worse physical health (lower PGP, lower SF10a) and mental health outcomes (lower PGM). While advanced age (-1.815; <0.001), and lower SES (0.871; 0.027) specifically predicted poorer physical function (lower SF10a). Fatigue (higher F4a) was seen more frequently among women (1.711; <0.001), and those with BM (1.142; 0.002); AM (1.768; 0.011), and higher SEC (0.478; 0.016).Cluster analysis of patients with AIRDs revealed 2 clusters (Figure 1C 1D); cluster 1 with low PGP, PGM, SF10 and high F4a; cluster 2 with high PGP, PGM, SF10 and low F4a. The clusters differed predominantly based on the frequency of comorbidities; any comorbidity (59.7% vs 41.8%; p<0.001), BM (28.5% vs 14.7%; 0.001); CM (4.5% vs 1.9%; <0.001), and AM (10.0% vs 4.0%; <0.001).Conclusion: Comorbidities complicate three-quarters of individuals living with AIRDs, and have an outsized impact on self-reported physical function, perceived fatigue, and QoL. Substantial regional differences call for further exploration of key drivers of this important aspect to allow optimized multidisciplinary and holistic care in anticipation of poorer outcomes.Reference: [1]Harrison C, Britt H, Miller G, Henderson J. Examining different measures of multimorbidity, using a large prospective cross-sectional study in Australian general practice. BMJ Open. 2014 Jul 1;4(7):e004694.
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  • Tan Grahn, Hooi Min, et al. (författare)
  • Roxithromycin potentiates the effects of chloroquine and mefloquine on multidrug-resistant Plasmodium falciparum in vitro
  • 2007
  • Ingår i: Experimental Parasitology. - : Elsevier BV. - 0014-4894. ; 115:4, s. 387-392
  • Tidskriftsartikel (refereegranskat)abstract
    • Chloroquine (CQ) and mefloquine (MQ) are no longer potent antimalarial drugs due to the emergence of resistant Plasmodium falciparum. Combination therapy has become the standard for many regimes in overcoming drug resistance. Roxithromycin (ROM), a known p-glycoprotein inhibitor, is reported to have antimalarial activity and it is hoped it will potentiate the effects of both CQ/MQ and reverse CQ/MQ-resistance. We assayed the effects of CQ and MQ individually and in combination with ROM on synchronized P. falciparum (Dd2 strain) cultures. The IC(50) values of CQ and MQ were 60.0+/-5.0 and 16.0+/-3.0 ng/ml; these were decreased substantially when combined with ROM. Isobolograms indicate that CQ-ROM combinations were relatively more synergistic (mean FICI 0.70) than MQ-ROM (mean FICI 0.85) with their synergistic effect at par with CQ-verapamil (VRP) (mean FICI 0.64) and MQ-VRP (mean FICI 0.60) combinations. We conclude that ROM potentiates the CQ/MQ response on multidrug-resistant P. falciparum.
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  • Yoshida, A., et al. (författare)
  • IMPAIRED HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES : A CROSS-SECTIONAL ANALYSIS FROM AN INTERNATIONAL SURVEY
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 952-953
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Comprehensive and large-scale assessment of health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) worldwide is lacking. The second COVID-19 vaccination in autoimmune disease (COVAD-2) study [1] is an international, multicentre, self-reported e-survey assessing several aspects of COVID-19 infection and vaccination as well as validated patient-reported outcome measures (PROMs) to outline patient experience in various autoimmune diseases (AIDs), with a particular focus on IIMs.Objectives: To investigate physical and mental health in a global cohort of IIM patients compared to those with non-IIM autoimmune inflammatory rheumatic diseases (AIRDs), non-rheumatic AIDs (NRAIDs), and those without AIDs (controls), using Patient-Reported Outcome Measurement Information System (PROMIS) global health data obtained from the COVAD-2 survey.Methods: Demographics, AID diagnoses, comorbidities, disease activity, treatments, and PROMs were extracted from the COVAD-2 database. The primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Secondary outcomes included PROMIS physical function short form-10a (PROMIS PF-10a), pain visual analogue scale (VAS), and PROMIS Fatigue-4a scores. Each outcome was compared between IIMs, non-IIM AIRDs, NRAIDs, and controls. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis.Results: A total of 10,502 complete responses from 1582 IIMs, 4700 non-IIM AIRDs, 545 NRAIDs, and 3675 controls, which accrued as of May 2022, were analysed. Patients with IIMs were older [59±14 (IIMs) vs. 48±14 (non-IIM AIRDs) vs. 45±14 (NRAIDs) vs. 40±14 (controls) years, p<0.001] and more likely to be Caucasian [82.7% (IIMs) vs. 53.2% (non-IIM AIRDs) vs. 62.4% (NRAIDs) vs. 34.5% (controls), p<0.001]. Among IIMs, dermatomyositis (DM) and juvenile DM were the most common (31.4%), followed by inclusion body myositis (IBM) (24.9%). Patients with IIMs were more likely to have comorbidities [68.1% (IIMs) vs. 45.7% (non-IIM AIRDs) vs. 45.1% (NRAIDs) vs. 26.3% (controls), p<0.001] including mental disorders [33.4% (IIMs) vs. 28.2% (non-IIM AIRDs) vs. 28.4% (NRAIDs) vs. 17.9% (controls), p<0.001].GPH median scores were lower in IIMs compared to NRAIDs or controls [13 (interquartile range 10–15) IIMs vs. 13 (11–15) non-IIM AIRDs vs. 15 (13–17) NRAIDs vs. 17 (15–18) controls, p<0.001] and PROMIS PF-10a median scores were the lowest in IIMs [34 (25–43) IIMs vs. 40 (34–46) non-IIM AIRDs vs. 47 (40–50) NRAIDs vs. 49 (45–50) controls, p<0.001]. GMH median scores were lower in AIDs including IIMs compared to controls [13 (10–15) IIMs vs. 13 (10–15) non-IIM AIRDs vs. 13 (11–16) NRAIDs vs. 15 (13–17) controls, p<0.001]. Pain VAS median scores were higher in AIDs compared to controls [3 (1–5) IIMs vs. 4 (2–6) non-IIM AIRDs vs. 2 (0–4) NRAIDs vs. 0 (0–2) controls, p<0.001]. Of note, PROMIS Fatigue-4a median scores were the highest in IIMs [11 (8–14) IIMs vs. 8 (10–14) non-IIM AIRDs vs. 9 (7–13) NRAIDs vs. 7 (4–10) controls, p<0.001].Multivariable regression analysis in IIMs identified older age, male sex, IBM, comorbidities including hypertension and diabetes, active disease, glucocorticoid use, increased pain and fatigue as the independent factors for lower GPH scores, whereas coexistence of interstitial lung disease, mental disorders including anxiety disorder and depression, active disease, increased pain and fatigue were the independent factors for lower GMH scores.Conclusion: Both physical and mental health are significantly impaired in patients with IIMs compared to those with non-IIM AIDs or those without AIDs. Our results call for greater attention to patient-reported experience and comorbidities including mental disorders to provide targeted approaches and optimise global well-being in patients with IIMs.
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  • Andreoli, L., et al. (författare)
  • COVID-19 VACCINE SAFETY DURING PREGNANCY AND BREASTFEEDING IN WOMEN WITH AUTOIMMUNE DISEASES : RESULTS FROM THE COVAD STUDY
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 56-57
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: COVID-19 vaccine hesitancy among pregnant and breastfeeding women with autoimmune diseases (AID) is often attributed to the fear of adverse events (AE) and disease flares (DF). No data are available regarding COVID-19 vaccine safety in this population.Objectives: We aimed at describing delayed-onset (>7 days) vaccine-related AE (minor and major), DF, and related AID treatment modifications from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.Methods: Among complete responses from 9201 participants as of June 21, 2022, 6787 (73.8%) were women. Six subgroups were identified upon diagnosis of AID vs healthy controls (HC) and their pregnancy/breastfeeding status at the time of any dose of vaccine (Figure 1).Results: Forty pregnant and 52 breastfeeding AID patients were identified and their vaccination rates (at least one dose) was 100% and 96.2%, respectively (Table 1). Overall AE, minor AE, and major AE were reported significantly more frequently by pregnant than non-pregnant patients (45% vs. 26%, p=0.01; 40% vs. 25.9%, p=0.03; 17.5% vs. 4.6%, p<0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18% of age- and disease-matched control patients (n=2315). All DF in pregnant/breastfeeding patients were managed with glucocorticoids and a fifth of them required initiation or change in immunosuppressive treatment.Conclusion: This study provides the first insights into the safety of COVID-19 vaccination during the antenatal period in women with AID. While AEs were more commonly reported by pregnant patients with AID, these were no higher than among pregnant healthy controls without AID. These observations are reassuring, likely to strengthen physician-patient communication and overcome hesitancy as the benefits for the mother and fetus by passive immunization are likely to overweigh the potential risks of AE and DF.Reference: [1]Fazal ZZ, et al; COVAD Study Group. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int 2022; 42:2151-2158.
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  • Holloway, A., et al. (författare)
  • EVALUATING GLOBAL PATTERNS IN TREATMENT AND PREVALENCE OF COMORBIDITIES IN SYSTEMIC LUPUS ERYTHEMATOSUS
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1456-1458
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Regional disparities in the management of systemic lupus erythematosus (SLE) are frequently described. Governance, funding, logistic barriers, and physician choice may be important determinants though scarce data from underrepresented regions limits our understanding.Objectives: To evaluate global patterns in treatment of SLE and identify the prevalence of comorbidities.Methods: We identified SLE patients from the COVAD 2 database, consisting of over 20,000 respondents worldwide. Healthy controls (HC) were included to assess population comorbidity levels. Demographics, treatment i.e., corticosteroids (CS), antimalarials, immunosuppressants (IS), cyclophosphamide and biologics plus comorbidity data was recorded. Country Human Development Index (HDI) classification, a composite index formulated by the United Nations to rank countries into tiers of development, was utilised.Results: 3323 HCs and 1167 SLE patients were included in analysis. Patients from low/medium HDI (lmHDI) countries were younger than those from high/very high HDI (hvhHDI) countries (median age 32, IQR 27-41 vs 41, IQR 32-52 years, p<0.0001). Disease duration was shorter in lmHDI countries (median 5, IQR 3-10 vs 10, IQR 5-19 years, p<0.0001).A higher proportion of SLE patients from lmHDI countries were on CS (73% vs 59%, p=0.0002), antimalarials (81% vs 68%, p=0.0002) and IS (66% vs 53%, p=0.0009) compared with patients from hvhHDI countries. Choice of IS varied with azathioprine prescribed more frequently in lmHDI countries (p=0.049). Biologics use was more common in hvhHDI countries (7% vs 2%, p=0.0055). Comorbidity prevalence was similar between groups, however when adjusted for age, patients with chronic kidney disease were significantly younger in lmHDI countries (36.67 vs 44.64 years, p=0.015), as were patients with coronary artery disease (35.7 vs. 44.6 years, p=0.015) and hypertension (41.5 vs 49.8 years, p=0.003). Results are detailed in Table 1.Conclusion: To our knowledge, this is the largest study evaluating treatment and comorbidity incidence in SLE populations based on country HDI. We identified striking differences in pharmacological management globally. Cardiovascular comorbidities were seen in younger patients and earlier in the disease course in lmHDI countries, suggestive of premature organ damage. This could be due to limited global access to high-cost medication and increasing access may improve outcomes. Our results call for review of cardiovascular risk guidelines and regional approaches to preventive action as well as pharmacological and non-pharmacological management of patients with established cardiovascular comorbidity.
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  • Hoste, E, et al. (författare)
  • OTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identity
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 5913-
  • Tidskriftsartikel (refereegranskat)abstract
    • OTULIN is a deubiquitinase that specifically cleaves linear ubiquitin chains. Here we demonstrate that the ablation ofOtulinselectively in keratinocytes causes inflammatory skin lesions that develop into verrucous carcinomas. Genetic deletion ofTnfr1, knockin expression of kinase-inactiveRipk1or keratinocyte-specific deletion ofFaddandMlklcompletely rescues mice with OTULIN deficiency from dermatitis and tumorigenesis, thereby identifying keratinocyte cell death as the driving force for inflammation. Single-cell RNA-sequencing comparing non-lesional and lesional skin reveals changes in epidermal stem cell identity in OTULIN-deficient keratinocytes prior to substantial immune cell infiltration. Keratinocytes lacking OTULIN display a type-1 interferon and IL-1β response signature, and genetic or pharmacologic inhibition of these cytokines partially inhibits skin inflammation. Finally, expression of a hypomorphic mutantOtulinallele, previously shown to cause OTULIN-related autoinflammatory syndrome in humans, induces a similar inflammatory phenotype, thus supporting the importance of OTULIN for restraining skin inflammation and maintaining immune homeostasis.
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  • Lee, S. Y., et al. (författare)
  • IDENTIFYING DETERMINANTS OF FAVOURABLE AND POOR PHYSICAL FUNCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS : RESULTS FROM AN INTERNATIONAL COLLABORATIVE STUDY
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1110-1112
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Systemic lupus erythematosus (SLE) can result in impaired daily physical function through various mechanisms including active disease, chronic damage, and mental health symptoms that are common in the disease. However, the key drivers of reduced physical function are poorly understood, and no large-scale global studies investigating this have been conducted to date.Objectives: To investigate key factors that contribute to impaired physical function in SLE globally.Methods: SLE patients were identified from the COVAD 2 database, a global register of more than 20,000 respondents. Healthy controls (HC) were included to compare differences in physical function using the Patient Reported Outcome Measurement Information System (PROMIS) questionnaire. Demographics, medication, comorbidities, disease activity, Global Physical Health (GPH) and Global Mental Health (GMH) were collected. Multivariable regression analysis was used to identify contributing factors to favourable or poor physical function (measured by PROMIS Physical Function shortform PF-10a score).Results: 979 SLE patients and 3358 HCs were included in analysis. Patients with SLE had significantly lower PF-10a score as compared to HCs (median 42, IQR 36-47 vs median 49, IQR 45-50, p<0.0001). Determinants of physical function status in patients with SLE are summarised in Table 1. Briefly, factors associated with poor physical function included increasing age (-0.042, 95% CI -0.069 to -0.015, p=0.002) and methotrexate use (-0.928, 95% CI -1.844 to -0.012, p=0.047). Diabetes (-1.862, 95% CI -3.481 to -0.243, p=0.024) and interstitial lung disease (ILD) (-2.441, 95% CI -4.366 to -0.517, p=0.013), but not asthma or COPD, also contributed to lower PF-10a score. From a mental health perspective, anxiety (-0.970, 95% CI -1.853 to -0.087, p=0.031) but not depression contributed to a lower physical function score. Higher Pain Visual Analogue Scales (VAS) (-2.889, 95% CI -3.107 to -2.671, p<0.001) and Fatigue VAS (-1.459, 95% CI -1.974 to -0.945, p<0.001) also contributed to lower PF-10 scores. Hydroxychloroquine use (0.844, 95% CI 0.190 to 1.498, p=0.012) and higher GPH score (2.287, 95% CI 2.079 to 2.494, p<0.001) were associated with favourable physical function.Conclusion: Patients with SLE show significantly reduced physical function compared with HCs. Key contributors to poor physical function include intercurrent diabetes and ILD. Screening for, and aggressive early treatment of these conditions may confer improved long-term function. As expected, higher levels of pain and fatigue were associated with poor physical function. Methotrexate use was also identified as a contributing factor to reduced function, which could represent its use in articular manifestations that limit physical function. Importantly, use of hydroxychloroquine was associated with favourable physical function, adding to the well-recognised benefits of this drug in SLE.
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  • Ravichandran, Ranjithkumar, et al. (författare)
  • Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications
  • 2016
  • Ingår i: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518. ; 4:2, s. 318-326
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.
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  • A, Lavanya, et al. (författare)
  • Smart energy monitoring and power quality performance based evaluation of 100-kW grid tied PV system
  • 2023
  • Ingår i: Heliyon. - 2405-8440. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Globally, the demand for energy from renewable sources is growing due to the increasing electricity consumption and the pollution of fossil fuels. The government has framed various policies to facilitate green energy generation, encouraging renewable energy source usage through PV installations in multiple sectors, including educational institutions. The primary objective of this paper is to propose a methodological approach for analysing the performance of the installed PV system on the rooftop of a university building in Tamil Nadu, India. The site selected is favourable for electricity generation from PV systems with an average global solar radiation of 5.82 kWh/m2day. Solar energy changes periodically with annual and daily variations and is not steady due to seasonal changes. The step-by-step performance assessment and the annual performance of the 100-kW solar PV system, which was instituted in 2019, with the forecasted parameters, are presented in this paper. Therefore, the assessment analysis is carried out in four phases: feasibility assessment, Energy yield assessment, Life cycle assessment, and Power quality assessment. To improve the solar PV output and efficiency, considering the solar irradiation, temperature, wind velocity, etc., PV yield is measured to evaluate the PV system's energy metrics. This paper also considers the carbon credits earned, solar power generated in the location, and the payback period. The power quality assessment is carried out in this paper to test the PV plant's compliance with effective grid integration.
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29.
  • Jain, Samatha M., et al. (författare)
  • Understanding the molecular mechanism responsible for developing therapeutic radiation-induced radioresistance of rectal cancer and improving the clinical outcomes of radiotherapy : A review
  • 2024
  • Ingår i: Cancer Biology & Therapy. - : Taylor & Francis. - 1538-4047 .- 1555-8576. ; 25:1
  • Forskningsöversikt (refereegranskat)abstract
    • Rectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as - the PI3K/AKT pathway, Wnt/β-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.
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30.
  • Olsson, E. Kihlgren, et al. (författare)
  • BREAKTHROUGH SARS-COV-2 INFECTION IN FULLY VACCINATED PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS : RESULTS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASE (COVAD) STUDY
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 540-541
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Although many studies have been conducted on COVID-19 in recent years, there are still unanswered questions regarding breakthrough infections (BTIs), particularly in patients with systemic lupus erythematosus (SLE).Objectives: This study aimed to determine the occurrence of breakthrough COVID-19 infections in patients with SLE versus other autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs).Methods: The study was based on data from the COVAD questionnaire which amassed a total of 10,783 complete responses from patients with SLE, AIRD, or nrAIRD, and HCs. After exclusion of individuals who were unvaccinated, those who received one vaccine dose only, and those with uncertain responses regarding the vaccine doses, a total of 9,595 patients formed the study population of the present investigation. If a COVID-19 infection occurred after the initial two vaccine doses and at least one booster dose (at least three doses in total, herein termed full vaccination), it was considered a BTI. Data were analysed using multivariable regression models. Statistically significant results were denoted by p values <0.05.Results: A total of 7,016/9,595 (73.1%) individuals were fully vaccinated. Among those, 1,002 (14.2%) reported at least one BTI, and 166 (2.3%) reported at least two BTIs. Among SLE patients, 867/1,218 (71.2%) were fully vaccinated. Among fully vaccinated SLE patients, 137 (15.8%) reported at least one BTI while 28 (3.2%) reported at least two BTIs. BTI frequencies in fully vaccinated SLE patients were comparable to those of other AIRDs (OR: 1.0; 95% CI: 0.8–1.3; p=0.447) and nrAIDS (OR: 0.9; 95% CI: 0.6–1.3; p=0.856) but higher compared with HCs (OR: 1.2; 95% CI: 1.0–1.6; p=0.022).For SLE patients with three vaccine doses, 113/137 (82.5%) reported at least one BTI while the corresponding number for four vaccine doses was 24/137 (17.5%). Compared with HCs (OR: 10.6; 95% CI: 1.2–93.0; p=0.032) and other AIRDs (OR: 3.5; 95% CI: 1.08–11.5; p=0.036), SLE patients showed higher frequencies of hospitalisation.AID multimorbidity was associated with a 15-fold increased risk for a need of advanced treatment for COVID-19 (OR: 15.3; 95% CI: 2.6–88.2; p=0.002).Conclusion: COVID-19 BTIs occurred in nearly 1 every 6th fully vaccinated patient with SLE, and 20% more frequently in this patient population compared with fully vaccinated HCs. Moreover, BTIs in SLE patients were more severe compared with BTIs in HCs or patients with AIRDs other than SLE, resulting in a greater need for hospitalisation. AID multimorbidity contributed to a more severe COVID-19 BTI requiring advanced management. These insights call for greater attention to vaccination in the vulnerable group of SLE patients, with appropriate risk stratification towards optimised vaccination strategies.
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31.
  • Prema, M., et al. (författare)
  • A new species of the xanthid crab genus Banareia A. Milne-Edwards, 1869 ( Crustacea: Brachyura: Xanthidae) from the Bay of Bengal, southeastern India
  • 2023
  • Ingår i: Raffles Bulletin of Zoology. - 0217-2445. ; 71, s. 387-399
  • Tidskriftsartikel (refereegranskat)abstract
    • A new species of the xanthid crab genus, Banareia A. Milne-Edwards, 1869, is described from India using morphological and molecular characters. The new species was collected from the bycatch of the Pazhayar fishing port, which receives trawl catches from the Bay of Bengal, off Tamil Nadu state, in southeastern India. Banareia metiguinotae, new species, is most similar to B. serenei Guinot, 1976, from Vietnam, in the general form and fresh colouration, but it differs mainly in the outline of the carapace, the form of the front, carapace anterolateral margin, ambulatory legs, and the male pleon and gonopods. The morphological description of the new species is further augmented by mitochondrial cytochrome oxidase subunit I (COI) sequence data. With the description of this new species, 17 species of Banareia are hereby recognised, with four species known from Indian territorial waters.
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32.
  • Prema, M., et al. (författare)
  • NEW RECORD OF THE SWIMMING CRAB CHARYBDIS (ARCHIAS) HONGKONGENSIS SHEN, 1934 (BRACHYURA, PORTUNIDAE) FROM INDIA
  • 2021
  • Ingår i: Crustaceana. - : Brill. - 0011-216X .- 1568-5403. ; 94:11-12, s. 1335-1343
  • Tidskriftsartikel (refereegranskat)abstract
    • Charybdis (Archias) hongkongensis Shen, 1934 was collected from the Indian coast of the Bay of Bengal and this is the first record from Indian waters. The distinct key characters of this species are: a relatively more produced last antero-lateral tooth, strongly convergent postero-lateral margins, and a smooth, rounded, reduced apex of the male first gonopod. This is the ninth member of Charybdis (Archias) Alcock, 1899 from Indian waters. The species is diagnosed and figured herein.
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33.
  • Rahaman, Hasibur, et al. (författare)
  • Improved ocean analysis for the Indian Ocean
  • 2019
  • Ingår i: Journal of operational oceanography. Publisher. - : Taylor & Francis. - 1755-876X .- 1755-8778. ; 12:1, s. 16-33
  • Tidskriftsartikel (refereegranskat)abstract
    • The National Centers for Environmental Prediction (NCEP) and the Indian National Centre for Ocean Information Services (INCOIS) produce global ocean analyses based on the Global Ocean Data Assimilation System (GODAS). This system uses a state of the art ocean general circulation model named moduler ocean model (MOM) and the 3D-Variational (3DVar) data assimilation technique. In this study we have evaluated the INCOIS-GODAS operational analysis products with an upgrade of the physical model from MOM4p0d to MOM4p1. Two experiments were performed with same atmospheric forcing fields:(i) using MOM4p0d (GODAS_p0), and (ii) using MOM4p1 (GODAS_p1). Observed temperature and salinity profiles were assimilated in both experiments. Validation with independent observations show improvement of sea surface temperature(SST), sea surface salinity (SSS) and surface currents in the new analysis GODAS_p1 as compared to the old analysis GODAS_p0.
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34.
  • Ravichandran, N., et al. (författare)
  • PREVALENCE, CHARACTERISTICS, AND PREDICTORS OF BREAKTHROUGH COVID-19 INFECTIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS : DATA FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASE (COVAD) STUDY
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 56-56
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Global data on COVID-19 breakthrough infections (BI) following COVID-19 vaccination among autoimmune rheumatic diseases (AIRDs) and especially rheumatoid arthritis (RA) is scarce.Objectives: This study aimed to examine the characteristics of COVID-19 BI among patients with RA and compare them with AIRDs and healthy controls (HCs).Methods: A global e-survey, January-May 2022, collected data on COVID-19 vaccination, and BI in patients with RA, AIRDs, non-rheumatic autoimmune disease (nrAIDs), and HCs. BI was defined as infection after both primary or booster vaccine doses. Severe BI was defined as the need for hospitalization, including intensive unit care, oxygen therapy, or advanced treatment in the form of monoclonal antibodies.Results: Of the 9595 vaccinated respondents of the e-survey, 3224 (33.6%) reported COVID-19. One BI was reported in 323/1802 (17.9%) patients with RA, 584/3869 (15.0%) patients with other AIRDs, and 467/3435 (13.5%) HCs. Similarly, second BI was reported by 280 (8.6%); 42 (2.3%) among RA, 90 (2.3%) among other AIRDs, and 124 (3.6%) among HCs.The prevalence of first BI in patients with RA was higher than that in those with AIRDs (OR=1.2; 95%CI=1.1-1.4; p=0.001) and HCs (OR=1.4; 95%CI=1.2-1.6; p<0.001), but similar to nrAIDs (p=0.783). The prevalence of second BI was lower in patients with RA than in HCs (OR=0.6; 95%CI=0.4-0.9; p=0.012) and nrAIDs (OR=0.4; 95%CI=0.2-0.7; p=0.004), but similar to AIRDs (p=0.991). When compared with HCs, patients with RA reported significantly higher joint pain, hospitalizations, and need for advanced treatment at first BI. Patients with RA from very high HDI countries had lower hazard of first BI than those from high HDI countries (HR=0.026; 95%CI=0.001-0.6; p=0.027). Rituximab use predicted more frequent hospitalization (OR=3.4; 95%CI=1.3-11.4; p=0.045) and severe BI (OR=3.0; 95%CI=1.2-7.3; p=0.014).Conclusion: Nearly one in five patients with RA reported BI. BI prevalence was higher in patients with RA and of higher severity than in HCs. Country HDI was an important determinant of outcomes, suggesting potential impact of environmental dynamics, local vaccination policy, and syndemic constructs that merit further exploration. Rituximab use predicted more frequent hospitalizations and more severe BI.
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35.
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36.
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37.
  • Taheri, Morteza, et al. (författare)
  • Features of hybrid laser-arc welding of GTD-111 superalloy compared to laser beam welding
  • 2022
  • Ingår i: Materials letters (General ed.). - : Elsevier B.V.. - 0167-577X .- 1873-4979. ; 309
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to influence the electric arc as a heat source on the welding pool created by the laser, hybrid laser-arc welding (HLAW) and laser beam welding (LBW) methods were utilized for the welding of GTD-111 superalloy. The results showed that the HLAW method, due to the creation of more heat input, provides the conditions for the exit of gaseous pores created in the weld metal. The electric arc, located 5 mm from the laser beam, re-melted the solidified grains in the keyhole and provided the conditions for nonhomogeneous nucleation of the equiaxed grains. 
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38.
  • Thandlam, Venugopal, et al. (författare)
  • Evaluation of MODIS/CERES downwelling shortwave and longwave radiation over global tropical oceans
  • 2016
  • Ingår i: Remote Sensing of the Atmosphere, Clouds, and Precipitation VI. - : SPIE-Intl Soc Optical Eng.
  • Konferensbidrag (refereegranskat)abstract
    • In the present work, we have evaluated the satellite-estimated daily downwelling shortwave (QI) and longwave (QA) radiation from Moderate Resolution Imaging Spectrometer (MODIS) /Clouds and the Earth's Radiant Energy System (CM) with moored buoy observations of Global Tropical MooredBuoy Array (GTMBA) during 2001-2009. The global observed mean of QI and QA in GTMBA(CM) are 228 (233) W/m2 and 410 (405) W/m2 respectively. The mean QI shows a positive bias (~3-7 W/m2) whereas QA underestimates with a mean negative bias of ~3-6 W/m2 in the tropical Pacific, Atlantic and the Indian Ocean. CM underestimates the buoy observed variability in both QI and QA in all the tropical oceans. The correlation coefficient (CC) values in QI (Qa) are 0.79(0.88) 0.79(0.84) and0.81(0.94) over the Pacific, Atlantic and Indian ocean respectively. The Root Mean Square Error(RMSE) values in QI ranged between 35-43 W/m2 with lowest values in the Atlantic Ocean and highest in the Indian Ocean. The RMSE values in QA are less as compared to QI and it is ~9 W/m2in all the tropical ocean. The spatial distributions of QI and QA shows seasonality with lower and higher values coinciding with the Inter-Tropical Convergence Zone(ITCZ) locations in the QI and QA
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39.
  • Thandlam, Venugopal, Mr. 1987-, et al. (författare)
  • Quantifying the role of antecedent Southwestern Indian Ocean capacitance on the summer monsoon rainfall variability over homogeneous regions of India
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of ocean variability is at a focal point in improving the weather and climate forecasts at different spatial and temporal scales. We study the effect of antecedent southwestern Indian Ocean mean sea level anomaly (MSLA) and sea surface temperature anomalies (SSTA) as a proxy to upper ocean heat capacitance on all India summer monsoon rainfall (AISMR) during 1993–2019. SSTA and MSLA over the southwestern Indian Ocean (SWIO) have been influenced by El Niño-Southern Oscillation (ENSO), the impact of ENSO-induced SWIO variability was low on rainfall variability over several homogeneous regions. Rainfall over northeast (NE) and North India (EI) has been modulated by ENSO-induced SSTA and MSLA over SWIO, thus effecting the total AISMR magnitude. The ENSO-induced changes in heat capacitance (SSTA and MSLA) over SWIO during antecedent months has less impact on west coast of India, central India and North India (NI) rainfall variability. The long-term trend in pre-monsoonal SSTA and MSLA over SWIO shows decreasing rainfall trend over NI, NE, and EI in the recent time. Furthermore, the cooler (warmer) anomaly over the western Indian Ocean affects rainfall variability adversely (favourably) due to the reversal of the wind pattern during the pre-monsoon period. While SSTA and MSLA are increasing in the SWIO, large-scale variability of these parameters during preceding winter and pre-monsoon months combined with surface winds could impact the inter-annual AISMR variability over homogeneous regions of India. Similarly, from an oceanic perspective, the antecedent heat capacitance over SWIO on an inter-annual time scale has been the key to the extreme monsoon rainfall variability.
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40.
  • Zhao, Baodan, et al. (författare)
  • High-efficiency perovskite-polymer bulk heterostructure light-emitting diodes
  • 2018
  • Ingår i: Nature Photonics. - : NATURE PUBLISHING GROUP. - 1749-4885 .- 1749-4893. ; 12:12, s. 783-
  • Tidskriftsartikel (refereegranskat)abstract
    • Perovskite-based optoelectronic devices are gaining much attention owing to their remarkable performance and low processing cost, particularly for solar cells. However, for perovskite light-emitting diodes, non-radiative charge recombination has limited the electroluminescence efficiency. Here we demonstrate perovskite-polymer bulk heterostructure light-emitting diodes exhibiting external quantum efficiencies of up to 20.1% (at current densities of 0.1-1 mA cm(-2)). The light-emitting diode emissive layer comprises quasi-two-dimensional and three-dimensional (2D/3D) perovskites and an insulating polymer. Photogenerated excitations migrate from quasi-2D to lower-energy sites within 1 ps, followed by radiative bimolecular recombination in the 3D regions. From near-unity external photoluminescence quantum efficiencies and transient kinetics of the emissive layer with and without charge-transport contacts, we find non-radiative recombination pathways to be effectively eliminated, consistent with optical models giving near 100% internal quantum efficiencies. Although the device brightness and stability (T-50 = 46 h in air at peak external quantum efficiency) require further improvement, our results indicate the significant potential of perovskite-based photon sources.
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