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  1. Article ; Online: Iron deficiency responses and integrated compensations in patients according to hereditary hemorrhagic telangiectasia

    Sharma, Lakshya / Almaghlouth, Fatma / Mckernan, Heidi / Springett, James / Tighe, Hannah C / Shovlin, Claire L

    Haematologica

    2024  Volume 109, Issue 3, Page(s) 958–962

    MeSH term(s) Humans ; Telangiectasia, Hereditary Hemorrhagic/genetics ; Smad4 Protein/genetics ; Endoglin ; Activin Receptors, Type II/genetics
    Chemical Substances SMAD4 protein, human ; Smad4 Protein ; ENG protein, human ; Endoglin ; ACVRL1 protein, human (EC 2.7.11.30) ; Activin Receptors, Type II (EC 2.7.11.30)
    Language English
    Publishing date 2024-03-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2022.282038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Intestinal Barrier Function in Health and Disease-Any role of SARS-CoV-2?

    Sharma, Lakshya / Riva, Antonio

    Microorganisms

    2020  Volume 8, Issue 11

    Abstract: Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system ... ...

    Abstract Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system and the gut barrier may be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and disruption of barrier functions or intestinal microbial dysbiosis may have an impact on the progression and severity of this new disease. In this review, we aim to provide an overview of current evidence on the involvement of gut alterations in human disease including COVID-19, with a prospective outlook on supportive therapeutic strategies that may be investigated to rescue intestinal barrier functions and possibly facilitate clinical improvement in these patients.
    Keywords covid19
    Language English
    Publishing date 2020-11-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms8111744
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Intestinal Barrier Function in Health and Disease—Any role of SARS-CoV-2?

    Lakshya Sharma / Antonio Riva

    Microorganisms, Vol 8, Iss 1744, p

    2020  Volume 1744

    Abstract: Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system ... ...

    Abstract Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system and the gut barrier may be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and disruption of barrier functions or intestinal microbial dysbiosis may have an impact on the progression and severity of this new disease. In this review, we aim to provide an overview of current evidence on the involvement of gut alterations in human disease including COVID-19, with a prospective outlook on supportive therapeutic strategies that may be investigated to rescue intestinal barrier functions and possibly facilitate clinical improvement in these patients.
    Keywords gastrointestinal ; COVID-19 ; SARS-CoV-2 ; microbiota ; gut barrier ; gut permeability ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Pulmonary arteriovenous malformations may be the only clinical criterion present in genetically confirmed hereditary haemorrhagic telangiectasia.

    Anderson, Emily / Sharma, Lakshya / Alsafi, Ali / Shovlin, Claire L

    Thorax

    2022  Volume 77, Issue 6, Page(s) 628–630

    Abstract: Pulmonary arteriovenous malformations (PAVMs) result in preventable complications demanding specialty care. Underlying hereditary haemorrhagic telangiectasia (HHT) can be identified by genetic testing, if the diagnosis is considered. Retrospectively ... ...

    Abstract Pulmonary arteriovenous malformations (PAVMs) result in preventable complications demanding specialty care. Underlying hereditary haemorrhagic telangiectasia (HHT) can be identified by genetic testing, if the diagnosis is considered. Retrospectively reviewing 152 unrelated adults with genetically confirmed HHT due to
    MeSH term(s) Activin Receptors, Type II/genetics ; Adult ; Arteriovenous Fistula ; Arteriovenous Malformations/complications ; Arteriovenous Malformations/diagnosis ; Arteriovenous Malformations/genetics ; Humans ; Pulmonary Artery/abnormalities ; Pulmonary Veins/abnormalities ; Retrospective Studies ; Telangiectasia, Hereditary Hemorrhagic/diagnosis ; Telangiectasia, Hereditary Hemorrhagic/genetics
    Chemical Substances ACVRL1 protein, human (EC 2.7.11.30) ; Activin Receptors, Type II (EC 2.7.11.30)
    Language English
    Publishing date 2022-02-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 204353-1
    ISSN 1468-3296 ; 0040-6376
    ISSN (online) 1468-3296
    ISSN 0040-6376
    DOI 10.1136/thoraxjnl-2021-218332
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Chemotherapy in Pregnancy: Assessing the Safety of Adriamycin Administration in Pregnancy Complicated by Breast Cancer.

    Nain, Priyanshu / Seth, Lakshya / Bell, Ashley Shawn / Raval, Priyanka / Sharma, Gyanendra / Bethel, Monique / Sharma, Garima / Guha, Avirup

    JACC. Case reports

    2023  Volume 28, Page(s) 102141

    Abstract: Pregnancy-associated breast cancer is challenging to treat. Treatment with chemotherapeutic agents such as anthracyclines poses a risk of cardiotoxicity, despite being considered safe after the second trimester of pregnancy. Management requires ... ...

    Abstract Pregnancy-associated breast cancer is challenging to treat. Treatment with chemotherapeutic agents such as anthracyclines poses a risk of cardiotoxicity, despite being considered safe after the second trimester of pregnancy. Management requires multidisciplinary comanagement with cardio-obstetrics, cardiology-oncology, maternal-fetal medicine, and oncology.
    Language English
    Publishing date 2023-11-12
    Publishing country Netherlands
    Document type Case Reports
    ISSN 2666-0849
    ISSN (online) 2666-0849
    DOI 10.1016/j.jaccas.2023.102141
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Intestinal Barrier Function in Health and Disease—Any role of SARS-CoV-2?

    Sharma, Lakshya Riva Antonio

    Microorganisms

    Abstract: Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system and ...

    Abstract Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system and the gut barrier may be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and disruption of barrier functions or intestinal microbial dysbiosis may have an impact on the progression and severity of this new disease In this review, we aim to provide an overview of current evidence on the involvement of gut alterations in human disease including COVID-19, with a prospective outlook on supportive therapeutic strategies that may be investigated to rescue intestinal barrier functions and possibly facilitate clinical improvement in these patients
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #918232
    Database COVID19

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  7. Article: Intestinal Barrier Function in Health and Disease—Any Role of SARS-CoV-2?

    Sharma, Lakshya / Riva, Antonio

    Microorganisms. 2020 Nov. 06, v. 8, no. 11

    2020  

    Abstract: Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system ... ...

    Abstract Alterations in the structure and function of the intestinal barrier play a role in the pathogenesis of a multitude of diseases. During the recent and ongoing coronavirus disease (COVID-19) pandemic, it has become clear that the gastrointestinal system and the gut barrier may be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and disruption of barrier functions or intestinal microbial dysbiosis may have an impact on the progression and severity of this new disease. In this review, we aim to provide an overview of current evidence on the involvement of gut alterations in human disease including COVID-19, with a prospective outlook on supportive therapeutic strategies that may be investigated to rescue intestinal barrier functions and possibly facilitate clinical improvement in these patients.
    Keywords Coronavirus infections ; Severe acute respiratory syndrome coronavirus ; absorption barrier ; dysbiosis ; human diseases ; intestines ; pandemic ; pathogenesis ; patients ; therapeutics ; viruses
    Language English
    Dates of publication 2020-1106
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-light
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms8111744
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: DNA variant classification-reconsidering "allele rarity" and "phenotype" criteria in ACMG/AMP guidelines.

    Davieson, Connor D / Joyce, Katie E / Sharma, Lakshya / Shovlin, Claire L

    European journal of medical genetics

    2021  Volume 64, Issue 10, Page(s) 104312

    Abstract: Recent guidance suggested modified DNA variant pathogenicity assignments based on genome-wide allele rarity. Different a priori probabilities of pathogenicity operate where patients already have clinical diagnoses, and are found to have a very rare ... ...

    Abstract Recent guidance suggested modified DNA variant pathogenicity assignments based on genome-wide allele rarity. Different a priori probabilities of pathogenicity operate where patients already have clinical diagnoses, and are found to have a very rare variant in a gene known to cause their disease, compared to predictive testing of a clinically unaffected individual. We tested new recommendations from the ClinGen Sequence Variant Interpretation Working Group for ClinVar-listed, loss-of-function variants meeting the very strong evidence of pathogenicity criterion [PVS1] in genes for 3 specific diseases where causal gene identification can modify clinical care of an individual- Von Willebrand disease, cystic fibrosis and hereditary haemorrhagic telangiectasia. Across these diseases, current rules leave 20/1,278 (1.6%) of loss-of-function variants as variants of uncertain significance (VUS that may not be reported to clinicians), and 207/1,278 (17.2%) as likely pathogenic. Applying the new ClinGen rule enabling PVS1 and the allele rarity criterion PM2 to delineate likely pathogenicity still left 8/1,278 (0.9%) as VUS (reflecting non-PVS1 calls by the submitters), and the majority of null alleles meeting PVS1 as merely likely pathogenic. We favour an approach whereby, for PVS1 variants in patients who personally meet the phenotypic PP4 criterion for a disease where casual variants are commonly family-specific, that PM2 is upgraded to permit a pathogenic call. Of 1,278 ClinVar-listed frameshift, nonsense and canonical splice site variants that met PVS1 in the 3 conditions, 16.0% (204/1,278) would be newly designated as pathogenic, avoiding misinterpretation outside of clinical genetics communities. We suggest further discussion around variant assessment across different clinical applications, potentially guided by PP4 alerts to distinguish personal versus family phenotypic history.
    MeSH term(s) Consensus Development Conferences as Topic ; Cystic Fibrosis/diagnosis ; Cystic Fibrosis/genetics ; Gene Frequency ; Genetic Testing/methods ; Genetic Testing/standards ; Humans ; Mutation ; Phenotype ; Practice Guidelines as Topic ; Telangiectasia, Hereditary Hemorrhagic/diagnosis ; Telangiectasia, Hereditary Hemorrhagic/genetics ; von Willebrand Diseases/diagnosis ; von Willebrand Diseases/genetics
    Language English
    Publishing date 2021-08-16
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2184135-4
    ISSN 1878-0849 ; 1769-7212
    ISSN (online) 1878-0849
    ISSN 1769-7212
    DOI 10.1016/j.ejmg.2021.104312
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  9. Book ; Online: GrapeQA

    Taunk, Dhaval / Khanna, Lakshya / Kandru, Pavan / Varma, Vasudeva / Sharma, Charu / Tapaswi, Makarand

    GRaph Augmentation and Pruning to Enhance Question-Answering

    2023  

    Abstract: Commonsense question-answering (QA) methods combine the power of pre-trained Language Models (LM) with the reasoning provided by Knowledge Graphs (KG). A typical approach collects nodes relevant to the QA pair from a KG to form a Working Graph (WG) ... ...

    Abstract Commonsense question-answering (QA) methods combine the power of pre-trained Language Models (LM) with the reasoning provided by Knowledge Graphs (KG). A typical approach collects nodes relevant to the QA pair from a KG to form a Working Graph (WG) followed by reasoning using Graph Neural Networks(GNNs). This faces two major challenges: (i) it is difficult to capture all the information from the QA in the WG, and (ii) the WG contains some irrelevant nodes from the KG. To address these, we propose GrapeQA with two simple improvements on the WG: (i) Prominent Entities for Graph Augmentation identifies relevant text chunks from the QA pair and augments the WG with corresponding latent representations from the LM, and (ii) Context-Aware Node Pruning removes nodes that are less relevant to the QA pair. We evaluate our results on OpenBookQA, CommonsenseQA and MedQA-USMLE and see that GrapeQA shows consistent improvements over its LM + KG predecessor (QA-GNN in particular) and large improvements on OpenBookQA.
    Keywords Computer Science - Computation and Language
    Publishing date 2023-03-22
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: Respiratory failure and sleep-disordered breathing in late-onset Pompe disease: a narrative review.

    Shah, Neeraj Mukesh / Sharma, Lakshya / Ganeshamoorthy, Santhosh / Kaltsakas, Georgios

    Journal of thoracic disease

    2020  Volume 12, Issue Suppl 2, Page(s) S235–S247

    Abstract: Late-onset Pompe disease (LOPD) is a rare autosomal recessive glycogen storage disease that results in accumulation of glycogen in muscle cells causing muscular weakness. It causes a progressive proximal myopathy, accompanied by respiratory muscle ... ...

    Abstract Late-onset Pompe disease (LOPD) is a rare autosomal recessive glycogen storage disease that results in accumulation of glycogen in muscle cells causing muscular weakness. It causes a progressive proximal myopathy, accompanied by respiratory muscle weakness, which can lead to ventilatory failure. In untreated LOPD, the most common cause of death is respiratory failure. Patients suffering from respiratory compromise may present with symptoms of sleep-disordered breathing (SDB) before overt signs of respiratory failure. Diaphragm weakness leads to nocturnal hypoventilation, which can result in sleep disruption. Both subjective and objective sleep quality can be impaired with associated excessive daytime sleepiness (EDS). Health-related quality of life worsens as sleep disturbance increases. The mainstay of treatment for SDB and respiratory failure in LOPD is non-invasive ventilation (NIV), which aims to ensure adequate ventilation, particularly during sleep, and prevent acute hypercapnic failure. These patients are at risk of acute deterioration due to lower respiratory tract infections; effective secretion clearance and vaccination against common pathogens is an important facet of care. Whilst disease-modifying enzyme replacement therapy (ERT) delays progression of locomotor dysfunction and prolongs life, its effect on respiratory function and SDB remains unclear. There are no data demonstrating the impact of ERT on sleep quality or SDB.
    Language English
    Publishing date 2020-11-10
    Publishing country China
    Document type Journal Article ; Review
    ZDB-ID 2573571-8
    ISSN 2077-6624 ; 2072-1439
    ISSN (online) 2077-6624
    ISSN 2072-1439
    DOI 10.21037/jtd-cus-2020-007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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