Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 551
Filter
1.
2.
Immunity ; 55(5):738-748, 2022.
Article in English | PubMed | ID: covidwho-1838897

ABSTRACT

The brutal toll of another viral pandemic can be blunted by investing now in research that uncovers mechanisms of broad-based immunity so we may have vaccines and therapeutics at the ready. We do not know exactly what pathogen may trigger the next wave or next pandemic. We do know, however, that the human immune system must respond and must be bolstered with effective vaccines and other therapeutics to preserve lives and livelihoods. These countermeasures must focus on features conserved among families of pathogens in order to be responsive against something yet to emerge. Here, we focus on immunological approaches to mitigate the impact of the next emerging virus pandemic by developing vaccines that elicit both broadly protective antibodies and T cells. Identifying human immune mechanisms of broad protection against virus families with pandemic potential will be our best defense for humanity in the future.

3.
Computers in Biology and Medicine ; 145, 2022.
Article in English | ProQuest Central | ID: covidwho-1838690

ABSTRACT

The causative agent of the COVID-19 pandemic, the SARS-CoV-2 virus has yielded multiple relevant mutations, many of which have branched into major variants. The Omicron variant has a huge similarity with the original viral strain (first COVID-19 strain from Wuhan). Among different genes, the highly variable orf8 gene is responsible for crucial host interactions and has undergone multiple mutations and indels. The sequence of the orf8 gene of the Omicron variant is, however, identical with the gene sequence of the wild type. orf8 modulates the host immunity making it easier for the virus to conceal itself and remain undetected. Variants seem to be deleting this gene without affecting the viral replication. While analyzing, we came across the conserved orf7a gene in the viral genome which exhibits a partial sequence homology as well as functional similarity with the SARS-CoV-2 orf8. Hence, we have proposed here in our hypothesis that, orf7a might be an alternative reserve of orf8 present in the virus which was compensating for the lost gene. A computational approach was adopted where we screened various miRNAs targeted against the orf8 gene. These miRNAs were then docked onto the orf8 mRNA sequences. The same set of miRNAs was then used to check for their binding affinity with the orf7a reference mRNA. Results showed that miRNAs targeting the orf8 had favorable shape complementarity and successfully docked with the orf7a gene as well. These findings provide a basis for developing new therapeutic approaches where both orf8 and orf7a can be targeted simultaneously.

4.
Cells ; 11(9):1490, 2022.
Article in English | ProQuest Central | ID: covidwho-1837098

ABSTRACT

γδ T cells, a small subset of T cells in blood, play a substantial role in influencing immunoregulatory and inflammatory processes. The functional impact of γδ T cells on angiogenesis in ischemic muscle tissue has never been reported and is the topic of the present work. Femoral artery ligation (FAL) was used to induce angiogenesis in the lower leg of γδ T cell depleted mice and wildtype and isotype antibody-treated control groups. Gastrocnemius muscle tissue was harvested 3 and 7 days after FAL and assessed using (immuno-)histological analyses. Hematoxylin and Eosin staining showed an increased area of tissue damage in γδ T cell depleted mice 7 days after FAL. Impaired angiogenesis was demonstrated by lower capillary to muscle fiber ratio and decreased number of proliferating endothelial cells (CD31+/BrdU+). γδ T cell depleted mice showed an increased number of total leukocytes (CD45+), neutrophils (MPO+) and neutrophil extracellular traps (NETs) (MPO+/CitH3+), without changes in the neutrophils to NETs ratio. Moreover, the depletion resulted in a higher macrophage count (DAPI/CD68+) caused by an increase in inflammatory M1-like macrophages (CD68+/MRC1−). Altogether, we show that depletion of γδ T cells leads to increased accumulation of leukocytes and M1-like macrophages, along with impaired angiogenesis.

5.
Organ Transplantation ; 13(3):325-332, 2022.
Article in Chinese | Academic Search Complete | ID: covidwho-1834996

ABSTRACT

Over the past 70 years, kidney transplantation has become not only the most mature but also the highest-success-rate surgery among all organ transplantation surgeries. However, the long-term survival of kidney transplant recipients is still challenged by such key factors as ischemia-reperfusion injury related to kidney transplantation, rejection, chronic renal allograft dysfunction, renal allograft fibrosis, immunosuppressive therapy, infections and others. Relevant fundamental and clinical studies have emerged endlessly. At the same time, the research related to kidney transplantation also becomes a new hot spot accordingly in the context of the normalization of novel coronavirus pneumonia. This article reviewed the cutting-edge hot spots in relation to the fundamental and clinical aspects of kidney transplantation together with relevant new techniques and new visions. The studies included in this article focused on the reports published by Chinese teams that are more applicable to the current situation of kidney transplantation in China, for the purpose of providing new thoughts and strategies for the diagnosis and treatment of kidney transplantation related issues in China. (English) [ FROM AUTHOR] 经过近 70 年的发展,肾移植已成为所有器官移植手术里最成熟,也是成功率最高的手术,但肾移 植相关缺血 - 再灌注损伤、排斥反应、慢性移植肾失功、移植肾纤维化、免疫抑制治疗与感染等仍是影响肾移植 受者长期生存的关键因素,相关的基础与临床研究层出不穷。同时,在新型冠状病毒肺炎疫情常态化的背景下, 与肾移植相关的研究也是一个新的热点。本文就 2021 年肾移植基础与临床相关的前沿热点以及肾移植相关的新 技术、新视野做一综述,且介绍的研究以中国团队发表的报道为主,更符合中国肾移植的实际情况,以期为我国 肾移植相关问题的诊疗提供新的思路和策略. (Chinese) [ FROM AUTHOR] Copyright of Organ Transplantation / Qi Guan Yi Zhi is the property of Organ Transplantation Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

6.
Hemato ; 2(3):441, 2021.
Article in English | ProQuest Central | ID: covidwho-1834787

ABSTRACT

In this paper, we explore the application of Chimeric Antigen Receptor (CAR) T cell therapy for the treatment of Acute Lymphocytic Leukaemia (ALL) by means of in silico experimentation, mathematical modelling through first-order Ordinary Differential Equations and nonlinear systems theory. By combining the latter with systems biology on cancer evolution we were able to establish a sufficient condition on the therapy dose to ensure complete response. The latter is illustrated across multiple numerical simulations when comparing three mathematically formulated administration protocols with one of a phase 1 dose-escalation trial on CAR-T cells for the treatment of ALL on children and young adults. Therefore, both our analytical and in silico results are consistent with real-life scenarios. Finally, our research indicates that tumour cells growth rate and the killing efficacy of the therapy are key factors in the designing of personalised strategies for cancer treatment.

7.
Cardiogenetics ; 11(1):28, 2021.
Article in English | ProQuest Central | ID: covidwho-1834715

ABSTRACT

Since late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) have become a worldwide threat to public health [1,2]. [...]the 49.4 kb haplotypes are almost absent in African and East Asian populations, but have a 30% frequency in South Asian and about an 8% frequency in European populations. [...]knowing individual genetic variation can help explain different susceptibility to SARS-CoV-2.

8.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822473

ABSTRACT

In response to the SARS-CoV-2 Delta variant, which partially escaped the vaccine-induced immunity provided by two doses of vaccination with CoronaVac (Sinovac), the National Vaccine Committee recommended the heterologous CoronaVac-ChAdOx1 (Oxford–AstraZeneca), a prime– boost vaccine regimen. This pilot study aimed to describe the immunogenicity and adverse events of the heterologous CoronaVac-ChAdOx1 regimen, in comparison with homologous CoronaVac, and homologous ChAdOx1. Between May and August 2021, we recruited a total of 354 participants from four vaccination groups: the CoronaVac-ChAdOx1 vaccinee (n = 155), the homologous CoronaVac vaccinee (n = 32), the homologous ChAdOx1 vaccinee (n = 47), and control group of COVID-19 patients (n = 120). Immunogenicity was evaluated by measuring the level of IgG antibodies against the receptor-binding domain (anti-SRBD) of the SARS-CoV-2 spike protein S1 subunit and the level of neutralizing antibodies (NAbs) against variants of concern (VOCs) using the plaque reduction neutralization test (PRNT) and pseudovirus neutralization test (pVNT). The safety profile was recorded by interviewing at the 1-month visit after vaccination. The anti-SRBD level after the second booster dose of the CoronaVac-ChAdOx1 group at 2 weeks was higher than 4 weeks. At 4 weeks after the second booster dose, the anti-SRBD level in the CoronaVac-ChAdOx1 group was significantly higher than ei-ther homologous CoronaVac, the homologous ChAdOx1 group, and Control group (p < 0.001). In the CoronaVac-ChAdOx1 group, the PRNT50 level against the wild-type (434.5 BAU/mL) was the high-est;followed by Alpha variant (80.4), Delta variant (67.4), and Beta variant (19.8). The PVNT50 level was also found to be at its highest against the wild-type (432.1);followed by Delta variants (178.3), Alpha variants (163.9), and Beta variant (42.2), respectively. The AEs in the CoronaVac-ChAdOx1 group were well tolerated and generally unremarkable. The CoronaVac-ChAdOx1 heterologous regimen induced higher immunogenicity and a tolerable safety profile. In a situation when only CoronaVac-ChAdOx1 vaccines are available, they should be considered for use in responding to the Delta variant.

9.
Clinical & Translational Immunology ; 11(4):15, 2022.
Article in English | Web of Science | ID: covidwho-1820890

ABSTRACT

Background and objectives. Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette-Guerin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS-CoV-2. Methods. This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with 7-irradiated SARS-CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry. Results. BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-alpha and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4(+) and CD8(+) T cells, and an activation of eosinophils in response to SARS-CoV-2. Conclusions. The immunomodulatory signature of BCG's off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19.

10.
Clinical Infectious Diseases ; : 5, 2022.
Article in English | Web of Science | ID: covidwho-1819773

ABSTRACT

COVID-19 breakthrough cases among vaccinated individuals demonstrate the value of measuring long-term immunity to SARS-CoV-2 and its variants. We demonstrate that anti-spike T-cell responses and IgG antibody levels are maintained but decrease over time and are lower in BNT162b2- versus mRNA-1273-vaccinated individuals. T-cell responses to the variants are relatively unaffected.

11.
Turkish Journal of Biology ; 46(2):105-117, 2022.
Article in English | Web of Science | ID: covidwho-1818260

ABSTRACT

Coronavirus disease 2019 (COVID-19) pandemic has been an important global interest that affected millions of people, and it requires a deep investigation of the disease immunology for developing further therapeutic applications. Adoptive T cell therapy promises to address T cell-dependent immune dysregulation in COVID-19 patients by the generation of specific T cell clones against virus-specific antigens. Additionally, targeting B cell-dependent protection through COVID-19 vaccines, which have been developed in the recent year, possessed sufficient prevention for spreading the virus, since the cases and deaths related to COVID-19 tend to decrease after the vaccination. However, adoptive cell therapies are now encouraging scientists to deal with pathological challenges like inadequate T cell-dependent immune response or lymphopenia, since they are the most frequent outcome of severe infection, especially in immunocompromized patients. In this review, the current knowledge of immunopathology of COVID-19 was aimed to be highlighted along with the T cell responses against SARS-CoV-2 to comprise a basis for therapeutics. Moreover, current therapeutics and treatment strategies for COVID-19 were discussed to evaluate possible agents. Furthermore, the use of adoptive T cell therapy representing an emerging therapeutic approach was purposed to be presented comprehensively against SARS-CoV-2 infection. Even though further studies are needed to fully understand T cell response against SARS-CoV-2 in order to develop therapies to provide long term and efficient protection, adoptive cell therapies now meet the demand for a large population of people who suffer immunocompromization, considering the previous usage of the technique for different infectious diseases.

12.
Frontiers in Medicine ; 9, 2022.
Article in English | EMBASE | ID: covidwho-1817977

ABSTRACT

SARS-CoV-2 is the causative agent of a new type of coronavirus infection, COVID-19, which has rapidly spread worldwide. The overall genome sequence homology between SARS-CoV-2 and SARS-CoV is 79%. However, the homology of the ORF8 protein between these two coronaviruses is low, at ~26%. Previously, it has been suggested that infection by the ORF8-deleted variant of SARS-CoV-2 results in less severe symptoms than in the case of wild-type SARS-CoV-2. Although we found that ORF8 is involved in the proteasome autoimmunity system, the precise role of ORF8 in infection and pathology has not been fully clarified. In this study, we determined a new network of ORF8-interacting proteins by performing in silico analysis of the binding proteins against the previously described 47 ORF8-binding proteins. We used as a dataset 431 human protein candidates from Uniprot that physically interacted with 47 ORF8-binding proteins, as identified using STRING. Homology and phylogenetic profile analyses of the protein dataset were performed on 446 eukaryotic species whose genome sequences were available in KEGG OC. Based on the phylogenetic profile results, clustering analysis was performed using Ward's method. Our phylogenetic profiling showed that the interactors of the ORF8-interacting proteins were clustered into three classes that were conserved across chordates (Class 1: 152 proteins), metazoans (Class 2: 163 proteins), and eukaryotes (Class 3: 114 proteins). Following the KEGG pathway analysis, classification of cellular localization, tissue-specific expression analysis, and a literature study on each class of the phylogenetic profiling cluster tree, we predicted that the following: protein members in Class 1 could contribute to COVID-19 pathogenesis via complement and coagulation cascades and could promote sarcoidosis;the members of Class 1 and 2, together, may contribute to the downregulation of Interferon-β;and Class 3 proteins are associated with endoplasmic reticulum stress and the degradation of human leukocyte antigen.

13.
Cytometry Part B - Clinical Cytometry ; 102(2):85-87, 2022.
Article in English | EMBASE | ID: covidwho-1813493
14.
Natural Volatiles & Essential Oils ; 8(5):816-821, 2021.
Article in English | GIM | ID: covidwho-1812797

ABSTRACT

Lymphocyte leukemia/lymphoma (ATLL) is a fringe T-cell harm brought about by human T-cell leukemia infection type. Lymphocyte leukemia (ATL) is an exceptionally forceful developed T-cell neoplasm related with human T-cell lymphotropic infection type 1 (HTLV-1) contamination, which influences around 10 million individuals on the planet. Of them, roughly 1-5% at last creates indicative ATL. Patient history: A 15 years male was admitted in AVBRH with complaint of fever, decrease appetite from 1 month, vomiting with blood tinged food particles and melena. Patient was diagnosed case of T-cell variant ALL. Before coming to AVBRH he was admitted to GMC Nagpur where he was diagnosed to had T-cell ALL with aberrant expression of CD10. He also had generalised lymphadenopathy and massive hepatosplenomegaly. He was advised blood transfusion but gives no H/O the same. Then he was discharged. After that patient developed malaena and blood tinged vomiting for which he came to AVBRH for further management. After his arrival, he was covid-19 positive so shifted to COVID ward. After two weeks, RTPCR status was negative then he shifted to PICU. . Clinical finding: The patient had done all necessary investigations by physician order. Medical Management: Patient was treated with IV. Fluids, platelet transfusion, chemotherapy, steroids, calcium gluconate, antibiotics, antacid, vit c and multivitamins. Nursing management: Administered fluid replacement i.e. D5, chemotherapy, platelet transfusion monitored all vital signs half hourly.

15.
Front Immunol ; 13:880190, 2022.
Article in English | PubMed | ID: covidwho-1809409

ABSTRACT

T-cells specifically bind antigens to induce adaptive immune responses using highly specific molecular recognition, and a diverse T-cell repertoire with expansion of antigen-specific clones can indicate robust immune responses after infection or vaccination. For patients with inflammatory bowel disease (IBD), a spectrum of chronic intestinal inflammatory diseases usually requiring immunomodulatory treatment, the T-cell response has not been well characterized. Understanding the patient factors that result in strong vaccination responses is critical to guiding vaccination schedules and identifying mechanisms of T-cell responses in IBD and other immune-mediated conditions. Here we used T-cell receptor sequencing to show that T-cell responses in an IBD cohort were influenced by demographic and immune factors, relative to a control cohort of health care workers (HCWs). Subjects were sampled at the time of SARS-CoV-2 vaccination, and longitudinally afterwards;TCR Vβ gene repertoires were sequenced and analyzed for COVID-19-specific clones. We observed significant differences in the overall strength of the T-cell response by age and vaccine type. We further stratified the T-cell response into Class-I- and Class-II-specific responses, showing that Ad26.COV2.S vector vaccine induced Class-I-biased T-cell responses, whereas mRNA vaccine types led to different responses, with mRNA-1273 vaccine inducing a more Class-I-deficient T-cell response compared to BNT162b2. Finally, we showed that these T-cell patterns were consistent with antibody levels from the same patients. Our results account for the surprising success of vaccination in nominally immuno-compromised IBD patients, while suggesting that a subset of IBD patients prone to deficiencies in T-cell response may warrant enhanced booster protocols.

16.
Front Immunol ; 13:832106, 2022.
Article in English | PubMed | ID: covidwho-1809389

ABSTRACT

Coronavirus disease 2019 (COVID-19) is the most devastating pandemic of the century, which is still far from over. The remarkable success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is the working hope, but the evolving variants are the huge concern that can turn the tide. Potential immune escape mutations (PIEMs) in the past and circulating variants were not studied at large scale (all available data). Hence, the conservation of antigenic determinants (epitopes) was analyzed in all available sequences of SARS-CoV-2 according to time (months), proteins, hosts, and variants. Numerous highly conserved B- and T-cell epitopes were identified in 24 proteins of SARS-CoV-2. A decrease in the conservation of epitopes with time was observed in almost all proteins, which was more rapid in neutralizing epitopes. Delta variant still has the highest PIEM in the circulating strains, which pose threat to the effectiveness of current vaccines. The inclusion of identified, highly conserved, and important epitopes in subunit vaccines can increase vaccine effectiveness against evolving variants. Trends in the conservation of epitopes in different proteins, hosts, and variants with time may also help to inspire the counter measure against the current pandemic.

17.
Am J Respir Crit Care Med ; 2022.
Article in English | PubMed | ID: covidwho-1807761
18.
Transplant Cell Ther ; 2022.
Article in English | PubMed | ID: covidwho-1804656

ABSTRACT

BACKGROUND: SARS-CoV-2 vaccines are capable of inducing combined humoral and cellular immunity. Which is more relevant for their potent protective effects is unclear, but isolated T-cell responses without seroconversion in healthy household members of COVID-patients suggest that T-cell responses effectively protect against clinical infection. Oncological patients have an outsize risk of unfavorable outcomes after SARS-CoV-2 infection and therefore were prioritized when vaccines first became available, although the quality of their immune response to vaccination was expected to be sub-optimal, as subsequent studies have confirmed. Inherently, patients with anti-CD19 CAR-T-mediated B-cell aplasia would be incapable of generating humoral responses, so that assessment of the vaccine-induced cellular immunity was all the more important to gauge whether the vaccine can induce meaningful protection. A salient difference between T-cell and humoral responses is the former's relative impassiveness to mutations of the antigen, as is more relevant than ever since the advent of the omicron variant. OBJECTIVE: The objective of this study was to assess in a cohort of juvenile CD19 CAR-T patients with enduring B-cell aplasia, the immune cell composition and spike protein-specific T-cell responses before and after the first and second doses of SARS-CoV-2 mRNA vaccine. STUDY DESIGN: The prospective study included all patients aged >12 years diagnosed with multiply relapsed B-cell precursor acute lymphoblastic leukaemia (ALL) and treated with anti-CD19 chimeric antigen receptor T-cell (CAR-T19) therapy in our center. The primary endpoint was the detection of cell-mediated and humoral response to vaccine (flow cytometry and anti-S immunoglobulin G, respectively). Secondary endpoints included the incidence of vaccine-related grade 3 or 4 adverse events, GvHD exacerbation, relapse and the influence of the vaccine on CAR-T cells and lymphocyte subset. RESULTS: Even though half of the patients exhibited sub-normal lymphocyte counts and marginal CD4/CD8 ratios, after two vaccinations all showed brisk T-cell responsiveness to spike protein, predominantly in the CD4 compartment, which was quantitatively well within the range of healthy controls. No severe vaccine-related grade 3 or 4 adverse events, GvHD exacerbation or relapse was observed in our cohort. CONCLUSION: We posit that SARS-CoV-2 mRNA vaccines induce meaningful cellular immunity in patients with isolated B-cell deficiency due to anti-CD19 CAR-T therapy.

19.
Journal of Medical Virology ; n/a(n/a), 2022.
Article in English | Wiley | ID: covidwho-1802459

ABSTRACT

The rapidly spreading SARS-CoV-2 Omicron variant contains more than 30 mutations that mediate escape from antibody responses elicited by prior infection or current vaccines. Fortunately, T cell responses are highly conserved in most individuals, but the impacts of mutations are not clear. Here, we showed that the T cell responses of individuals who underwent booster vaccination with CoronaVac were largely protective against the SARS-CoV-2 Omicron spike protein. To specifically estimate the impact of Omicron mutations on vaccinated participants, 16 peptides derived from the spike protein of the ancestral virus or Omicron strain with mutations were used to stimulate peripheral blood mononuclear cells (PBMCs) from the volunteers. Compared with the administration of two doses of vaccine, booster vaccination substantially enhanced T cell activation in response to both the ancestral and Omicron epitopes, although the enhancement was slightly weakened by the Omicron mutations. Then, the peptides derived from these spike proteins were used separately to stimulate PBMCs. Interestingly, compared with the ancestral peptides, only the peptides with the G339D or N440K mutation were detected to significantly destabilize the T cell response. Although more participants need to be evaluated to confirm this conclusion, our study nonetheless estimates the impacts of mutations on T cell responses to the SARS-CoV-2 Omicron variant.This article is protected by copyright. All rights reserved.

20.
International Journal of Infectious Diseases ; 2022.
Article in English | ScienceDirect | ID: covidwho-1799913

ABSTRACT

Objectives. We assessed vaccination-induced antibody and cellular responses against spike from the ancestral strain and from the delta (δ) SARS-CoV-2 variant in patients with Immune Mediated Inflammatory Diseases (IMID) on immunosuppressive therapy in comparison with immunocompetent subjects. Methods. We enrolled IMID patients and immunocompetent subjects having completed the vaccination schedule within 4-6 months from the first dose. The Interferon (IFN)-γ-response to spike peptides derived from the ancestral and the δ SARS-CoV-2 were measured by ELISA. Anti-RBD IgG antibodies were also evaluated. Results. We enrolled 43 IMID patients and 9 immunocompetent subjects. No significant differences were found comparing the specific immune response (IFN-γ) between IMID patients and immunocompetent subjects to the ancestral (p=0.36) or delta peptide pool (p=0.51). Nevertheless, IFN-γ-specific response to the ancestral or to the δ pools was reduced in subjects taking CTLA4-IgG or TNF-α inhibitors compared to subjects treated with IL-6 inhibitors or DMARDs. Regarding the antibody response, no significant differences were observed between IMID and immunocompetent individuals. Conclusions. Cellular responses to δ SARS-CoV-2 variant remain largely intact in IMID patients. However, the magnitude of these responses are dependent on the specific IMID immune suppressive regimen. Serological response was also similar among the IMID and control groups.

SELECTION OF CITATIONS
SEARCH DETAIL