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Artikel ; Online: Latent tuberculosis prevalence, diagnosis and treatment in Multiple Sclerosis as a strategy for reducing infection reactivation during immunosuppressant therapy.

Reis, Gelvana Flávio Barreto / de Castro, Andrea de Carvalho Anacleto Ferrari / Berezin, Eitan Naaman

Multiple sclerosis and related disorders

2024 Band 86, Seite(n) 105632

Abstract: Background: Tuberculosis is an infectious disease with a risk of reactivation in Multiple Sclerosis patients on immunosuppressant therapy. Diagnosis and treatment of Latent Tuberculosis Infection (LTBI) prevents the infection.: Objective: To diagnose ...

Abstract	Background: Tuberculosis is an infectious disease with a risk of reactivation in Multiple Sclerosis patients on immunosuppressant therapy. Diagnosis and treatment of Latent Tuberculosis Infection (LTBI) prevents the infection. Objective: To diagnose and treat LTBI in Multiple Sclerosis (MS). Methods: Cross-sectional study of the prevalence and treatment of LTBI in MS, between February 2021 and June 2023. LTBI was defined as an absence of symptoms, positive PPD or IGRA and normal chest X-ray. Results: Of the 58 patients with MS, 17 (29.3 %) were diagnosed with LTBI, 15 with PPD > 5 mm and 2 with positive IGRA, 10 (58.8 %) female and 7 (41.1 %) male, mean age of 41.3 (SD ±13.4) years. All patients with LTBI were treated with immunomodulators or immunosuppressants: Fingolimod 5 (29.4 %), Natalizumab 5 (29.4 %), Cladribine 2 (11.8 %), Glatiramer 2 (11.8 %), Ocrelizumab 2 (11.8 %), and Interferon beta 1 (5.9 %). Steroids therapy for relapses, were used in 5/17 (93.8 %) with LTBI and 30/37 (81.1 %) without LTBI. To treat LTBI, 11 (64.7 %) received Isoniazid and 6 (35.3 %) Isoniazid plus Rifapentine. Hepatotoxicity occurred in 3 (17.6 %) with INH. There were no interruptions of ILTB treatment during the study. Conclusion: The prevalence of LTBI was found to be high and treatment proved safe.
Mesh-Begriff(e)	Humans ; Female ; Latent Tuberculosis/diagnosis ; Latent Tuberculosis/epidemiology ; Male ; Immunosuppressive Agents/adverse effects ; Adult ; Cross-Sectional Studies ; Prevalence ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/epidemiology ; Middle Aged
Chemische Substanzen	Immunosuppressive Agents
Sprache	Englisch
Erscheinungsdatum	2024-04-15
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2024.105632
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Transcriptional analysis links B cells and TERT expression to favorable prognosis in head and neck cancer.

Xian, Su / Dosset, Magalie / Castro, Andrea / Carter, Hannah / Zanetti, Maurizio

PNAS nexus

2023 Band 2, Heft 3, Seite(n) pgad046

Abstract: Telomerase reverse transcriptase (TERT) is a conserved self-tumor antigen overexpressed in ∼85% of tumor cells and is immunogenic in cancer patients. The effect of TERT expression on the regulation of intratumor adaptive immunity has not yet been ... ...

Abstract	Telomerase reverse transcriptase (TERT) is a conserved self-tumor antigen overexpressed in ∼85% of tumor cells and is immunogenic in cancer patients. The effect of TERT expression on the regulation of intratumor adaptive immunity has not yet been investigated. We used RNA sequencing data from The Cancer Genome Atlas (TCGA) in 11 solid tumor types to investigate potential interactions between TERT expression, and B and T cell infiltrate in the tumor microenvironment. We found a positive correlation between TERT expression, B and T cells in four cancer types with the strongest association in head and neck squamous cell carcinoma (HSNCC). In HNSCC a B
Sprache	Englisch
Erscheinungsdatum	2023-02-10
Erscheinungsland	England
Dokumenttyp	Journal Article
ISSN	2752-6542
ISSN (online)	2752-6542
DOI	10.1093/pnasnexus/pgad046
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Mutagenic exposures shape immunotherapy responses.

Castro, Andrea / Carter, Hannah

Nature cancer

2020 Band 1, Heft 12, Seite(n) 1132–1133

Mesh-Begriff(e)	Immunotherapy/adverse effects ; Mutagenesis ; Mutagenicity Tests ; Mutagens
Chemische Substanzen	Mutagens
Sprache	Englisch
Erscheinungsdatum	2020-11-16
Erscheinungsland	England
Dokumenttyp	Journal Article ; Comment
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-020-00153-w
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Integrated germline and somatic features reveal divergent immune pathways driving ICB response.

Sears, Timothy / Pagadala, Meghana / Castro, Andrea / Lee, Ko-Han / Kong, JungHo / Tanaka, Kairi / Lippman, Scott / Zanetti, Maurizio / Carter, Hannah

bioRxiv : the preprint server for biology

2024

Abstract: Immune Checkpoint Blockade (ICB) has revolutionized cancer treatment, however mechanisms determining patient response remain poorly understood. Here we used machine learning to predict ICB response from germline and somatic biomarkers and interpreted the ...

Abstract	Immune Checkpoint Blockade (ICB) has revolutionized cancer treatment, however mechanisms determining patient response remain poorly understood. Here we used machine learning to predict ICB response from germline and somatic biomarkers and interpreted the learned model to uncover putative mechanisms driving superior outcomes. Patients with higher T follicular helper infiltrates were robust to defects in the class-I Major Histocompatibility Complex (MHC-I). Further investigation uncovered different ICB responses in MHC-I versus MHC-II neoantigen reliant tumors across patients. Despite similar response rates, MHC-II reliant responses were associated with significantly longer durable clinical benefit (Discovery: Median OS=63.6 vs. 34.5 months P=0.0074; Validation: Median OS=37.5 vs. 33.1 months, P=0.040). Characteristics of the tumor immune microenvironment reflected MHC neoantigen reliance, and analysis of immune checkpoints revealed LAG3 as a potential target in MHC-II but not MHC-I reliant responses. This study highlights the value of interpretable machine learning models in elucidating the biological basis of therapy responses.
Sprache	Englisch
Erscheinungsdatum	2024-01-15
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2024.01.12.575430
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Relative performance evaluation of four bleeding risk scores in atrial fibrillation patients. What does the new DOAC score provide?

Abu-Assi, Emad / Lizancos Castro, Andrea / Cespón-Fernández, María / González-Bermúdez, Inmaculada / Raposeiras Roubin, Sergio

International journal of cardiology

2024 , Seite(n) 132018

Abstract: Background: Recently, the direct oral anticoagulant (DOAC) score was developed and better predicted major bleeding in DOAC-treated patients with atrial fibrillation (AF) than HASBLED did. Little is known on the new score's performance regarding other ... ...

Abstract	Background: Recently, the direct oral anticoagulant (DOAC) score was developed and better predicted major bleeding in DOAC-treated patients with atrial fibrillation (AF) than HASBLED did. Little is known on the new score's performance regarding other bleeding risk in AF. Methods: We studied 14,672 patients diagnosed with AF between 2014 and 2018. During follow-up, we assessed the performance of DOAC score compared with the HASBLED, ORBIT and SWISS scores at predicting major bleeding in DOACs and non-DOACs users. Discrimination, calibration and decision curve analysis (DCA) were used to assess the risk scorer's performance. Results: There were 1484 (10.1%) patients on DOACs, 9730 on vitamin K antagonist (VKA), and 3458 on non-oral anticoagulants. Over a median of 3.5 years of follow-up, 79 major bleedings occurred in the DOAC patients, and 486 in the VKA patients (cumulative incidences = 7.4 and 13.9 per 100 patient-years, respectively). Amongst the DOAC patients, the DOAC score discrimination was moderate (C-statistic = 0.711), but significantly higher than HASBLED (C = 0.640; p = 0.03), ORBIT (C = 0.660; p = 0.04), and SWISS scores (C = 0.637; p = 0.002). The DCA showed higher net benefit using DOAC score compared with the remaining scores. In the VKA patients, DOAC score showed the highest discrimination (c-statistic = 0.709), followed by ORBIT (C = 0.692; p = 0.07), HASBLED and SWISS (C = 0.635 and 0.624, respectively; p < 0.01). All risk scores calibrated well, although HASBLED showed relatively poor calibration. Conclusions: The new DOAC bleeding risk score is a valid and reasonable predictor of major bleeding over a median of 3.5 years of follow-up. Physicians can be reassured about the applicability of DOAC score for bleeding risk stratification in AF patients. Registration: URL: https://www. Clinicaltrials: gov; Unique identifier: NCT04364516.
Sprache	Englisch
Erscheinungsdatum	2024-04-03
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2024.132018
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The economic impact of the COVID-19 pandemic on ethnic minorities in Manchester: lessons from the early stage of the pandemic.

Wiśniowski, Arkadiusz / Allen, Ruth / Aparicio-Castro, Andrea / Olsen, Wendy / Islam, Maydul

Frontiers in sociology

2023 Band 8, Seite(n) 1139258

Abstract: This review summarizes the economic impacts of the pandemic on ethnic minorities, focusing on the city of Manchester. It utilizes multiple reporting sources to explore various dimensions of the economic shock in the UK, linking this to studies of pre- ... ...

Abstract	This review summarizes the economic impacts of the pandemic on ethnic minorities, focusing on the city of Manchester. It utilizes multiple reporting sources to explore various dimensions of the economic shock in the UK, linking this to studies of pre-COVID-19 economic and ethnic composition in Manchester and in the combined authority area of Greater Manchester. We then make inferences about the pandemic's short-term impact specific to the city region. Greater Manchester has seen some of the highest rates of COVID-19 and as a result faced particularly stringent "lockdown" regulations. Manchester is the sixth most deprived Local Authority in England, according to 2019 English Indices of Multiple Deprivation. As a consequence, many neighborhoods in the city were always going to be less resilient to the economic shock caused by the pandemic compared with other, less-deprived, areas. Particular challenges for Manchester include the high rates of poor health, low-paid work, low qualifications, poor housing conditions and overcrowding. Ethnic minority groups also faced disparities long before the onset of the pandemic. Within the UK, ethnic minorities were found to be most disadvantaged in terms of employment and housing-particularly in large urban areas containing traditional settlement areas for ethnic minorities. Further, all Black, Asian, and Minority ethnic (BAME) groups in Greater Manchester were less likely to be employed pre-pandemic compared with White people. For example, people of Pakistani and Bangladeshi ethnic backgrounds, especially women, have the lowest levels of employment in Greater Manchester. Finally, unprecedented cuts to public spending as a result of austerity have also disproportionately affected women of an ethnic minority background alongside disabled people, the young and those with no or low-level qualifications. This environment has created and sustained a multiplicative disadvantage for Manchester's ethnic minority residents through the course of the COVID-19 pandemic.
Sprache	Englisch
Erscheinungsdatum	2023-05-19
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Review
ISSN	2297-7775
ISSN (online)	2297-7775
DOI	10.3389/fsoc.2023.1139258
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Primary Leptomeningeal B-cell Lymphoma in an Immunocompetent Adult: Case Report.

Calderon-Castro, Andrea / Enciso, Leonardo / Tejada-Cabrera, Rafael

Cureus

2021 Band 13, Heft 11, Seite(n) e19619

Abstract: Primary leptomeningeal lymphoma (PLML) is a rare disease, comprising less than 1% of all lymphomas. Clinical manifestations include headache, encephalopathy, ataxia, cranial nerve palsy, and myelitis. Diagnosis requires a combination of magnetic ... ...

Abstract	Primary leptomeningeal lymphoma (PLML) is a rare disease, comprising less than 1% of all lymphomas. Clinical manifestations include headache, encephalopathy, ataxia, cranial nerve palsy, and myelitis. Diagnosis requires a combination of magnetic resonance images (MRI), cytology, flow cytometry of cerebrospinal fluid (CSF), and an extensive workup to rule out systemic lymphoma. We describe the case of a 49-year-old man who developed subacute onset headache, encephalopathy, and blindness. Whole-body examinations, including a bone marrow trephine biopsy, excluded systemic lymphoma. Brain MRI showed leptomeningeal enhancement. Cytology and flow cytometry of CSF found a clonal B-cell population making a diagnosis of PLML. He began treatment with rituximab and high-dose methotrexate (HD-MTX), with progressive clinical improvement. CSF analysis after two cycles and one intrathecal methotrexate dose was normal. Brain and spinal MRI images plus CSF analysis, along with an extensive workup to exclude systemic lymphoma, are necessary to diagnose PLM. Early treatment with HD-MTX alone or in combination with rituximab improves clinical outcomes.
Sprache	Englisch
Erscheinungsdatum	2021-11-16
Erscheinungsland	United States
Dokumenttyp	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.19619
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Neoantigen Controversies.

Castro, Andrea / Zanetti, Maurizio / Carter, Hannah

Annual review of biomedical data science

2021 Band 4, Seite(n) 227–253

Abstract: Next-generation sequencing technologies have revolutionized our ability to catalog the landscape of somatic mutations in tumor genomes. These mutations can sometimes create so-called neoantigens, which allow the immune system to detect and eliminate ... ...

Abstract	Next-generation sequencing technologies have revolutionized our ability to catalog the landscape of somatic mutations in tumor genomes. These mutations can sometimes create so-called neoantigens, which allow the immune system to detect and eliminate tumor cells. However, efforts that stimulate the immune system to eliminate tumors based on their molecular differences have had less success than has been hoped for, and there are conflicting reports about the role of neoantigens in the success of this approach. Here we review some of the conflicting evidence in the literature and highlight key aspects of the tumor-immune interface that are emerging as major determinants of whether mutation-derived neoantigens will contribute to an immunotherapy response. Accounting for these factors is expected to improve success rates of future immunotherapy approaches.
Mesh-Begriff(e)	Antigens, Neoplasm/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunotherapy ; Mutation ; Neoplasms/genetics
Chemische Substanzen	Antigens, Neoplasm
Sprache	Englisch
Erscheinungsdatum	2021-05-11
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	2574-3414
ISSN (online)	2574-3414
DOI	10.1146/annurev-biodatasci-092820-112713
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: In silico analysis suggests less effective MHC-II presentation of SARS-CoV-2 RBM peptides: Implication for neutralizing antibody responses.

Castro, Andrea / Ozturk, Kivilcim / Zanetti, Maurizio / Carter, Hannah

PloS one

2021 Band 16, Heft 2, Seite(n) e0246731

Abstract: SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for ... ...

Abstract	SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.
Mesh-Begriff(e)	Amino Acid Motifs ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antibody Formation ; B-Lymphocytes/immunology ; COVID-19/immunology ; Computer Simulation ; Epitopes, B-Lymphocyte/chemistry ; Epitopes, B-Lymphocyte/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Models, Molecular ; Peptides/chemistry ; Peptides/immunology ; SARS-CoV-2/chemistry ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/immunology ; T-Lymphocytes/immunology
Chemische Substanzen	Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes, B-Lymphocyte ; Histocompatibility Antigens Class II ; Peptides ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Sprache	Englisch
Erscheinungsdatum	2021-02-11
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0246731
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: MHC-II constrains the natural neutralizing antibody response to the SARS-CoV-2 spike RBM in humans.

Castro, Andrea / Ozturk, Kivilcim / Zanetti, Maurizio / Carter, Hannah

bioRxiv : the preprint server for biology

2020

Abstract	SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.
Sprache	Englisch
Erscheinungsdatum	2020-12-28
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2020.12.26.424449
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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