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  1. Article ; Online: Evaluating Hymenoptera Venom Allergy Severity: A Data-Centric Comparison of Grading Instruments.

    Kačar, Mark / Košnik, Mitja

    International archives of allergy and immunology

    2024  , Page(s) 1–10

    Abstract: Introduction: While a consensus seems to have been reached with regard to the definition of anaphylaxis, there is no universal instrument for scoring allergic reaction severity despite more than 30 having been proposed by the time of writing. This ... ...

    Abstract Introduction: While a consensus seems to have been reached with regard to the definition of anaphylaxis, there is no universal instrument for scoring allergic reaction severity despite more than 30 having been proposed by the time of writing. This severely hampers comparison of data between studies. While scales have been compared with regard to their utility in grading food-related reactions, no such comparisons have been made for Hymenoptera venom-associated reactions.
    Methods: The study conducted a retrospective analysis to compare the severity of Hymenoptera venom allergy reactions in 104 participants with suspected Hymenoptera venom allergy. The study applied six grading instruments to each reaction, also evaluating them against the NIAID/FAAN anaphylaxis criteria. Sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) for identifying anaphylaxis were calculated. Severity scales were simplified into "mild," "moderate," and "severe" categories. The most common severity grade across the five scales was determined using a custom function to establish a consensus severity grade.
    Results: The most common culprit insects were honeybees (49.0%). Among the 88 participants with generalized reactions, the highest proportion had involvement of four organ systems. The scales showed high specificity for detecting anaphylaxis, especially when using higher grades of the Mueller, WAO, and Dribin scales. The diagnostic yields (AUC) varied, with the WAO scale having the highest AUC (0.94) for grades 3, 4, and 5. Spearman correlation analysis showed the strongest correlations seen between the Brown and Dribin, Ring and Messmer and Dribin, and Ring and Messmer and Reisman scales. The lowest correlations were observed with the Mueller scale when paired with the WAO, Reisman, and Dribin scales. An inter-rater reliability analysis showed substantial agreement between scales with the same number of grading levels. The agreement was highest for the Brown and Dribin scales, indicating a strong consistency in reaction severity classification across different instruments.
    Conclusion: While all instruments were effective in stratifying reactions, they showed limitations in differentiating milder phenotypes. The Brown and Dribin scales stood out for their high agreement with the consensus score and sensitivity in identifying anaphylaxis. Our findings suggest that adopting either of these scales could significantly unify the reporting of allergic reactions. We believe the format of an instrument should be tailored to its intended purpose, with clinical decision aids being simpler and research tools being more detailed.
    Language English
    Publishing date 2024-03-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1108932-5
    ISSN 1423-0097 ; 1018-2438
    ISSN (online) 1423-0097
    ISSN 1018-2438
    DOI 10.1159/000537680
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Clonal mast cell disorders and hereditary α-tryptasemia as risk factors for anaphylaxis.

    Kačar, Mark / Rijavec, Matija / Šelb, Julij / Korošec, Peter

    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

    2023  Volume 53, Issue 4, Page(s) 392–404

    Abstract: The association between Hymenoptera venom-triggered anaphylaxis (HVA) and clonal mast cell-related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood screening for KIT p.D816V missense variant have revealed the ...

    Abstract The association between Hymenoptera venom-triggered anaphylaxis (HVA) and clonal mast cell-related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood screening for KIT p.D816V missense variant have revealed the true extent of this clinical association whilst adding to our understanding of the underlying aetiology. Thus, recent large studies highlighted the presence of KIT p.D816V among 18.2% and 23% of patients with severe Hymenoptera venom-triggered anaphylaxis. A significant proportion of those patients have normal serum basal tryptase (BST) levels, with no cutaneous findings such as urticaria pigmentosa or other systemic findings such as organomegaly that would have suggested the presence of cMCD. These findings of an increased prevalence suggest that the impact of cMCD on anaphylaxis could be clinically underestimated and that the leading question for clinicians could be changed from 'how many patients with cMCD have anaphylaxis?' to 'how many patients with anaphylaxis have cMCD?'. The discovery of hereditary α-tryptasemia (HαT)-a genetic trait caused by an increased copy number of the Tryptase Alpha/Beta 1 (TPSAB1) gene-, first described in 2016, is now known to underlie the majority of cases of elevated BST outside of cMCD and chronic kidney disease. HαT is the first common heritable genetic modifier of anaphylaxis described, and it is associated with increased risk for severe HVA (relative risk = 2.0), idiopathic anaphylaxis, and an increased prevalence of anaphylaxis in patients with cMCD, possibly due to the unique activity profile of α/β -tryptase heterotetramers that may potentiate immediate hypersensitivity reaction severity. Our narrative review aims to highlight recent research to have increased our understanding of cMCD and HαT, through recent lessons learned from studying their association with HVA. Additionally, we examined the studies of mast cell-related disorders in food and drug allergy in an effort to determine whether one should also consider cMCD and/or HαT in cases of severe anaphylaxis triggered by food or drugs.
    MeSH term(s) Humans ; Anaphylaxis/epidemiology ; Anaphylaxis/etiology ; Anaphylaxis/diagnosis ; Tryptases/genetics ; Mast Cells ; Mastocytosis/complications ; Mastocytosis/genetics ; Mastocytosis/diagnosis ; Arthropod Venoms ; Risk Factors
    Chemical Substances Tryptases (EC 3.4.21.59) ; Arthropod Venoms
    Language English
    Publishing date 2023-01-18
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 645204-8
    ISSN 1365-2222 ; 0954-7894 ; 0960-2178
    ISSN (online) 1365-2222
    ISSN 0954-7894 ; 0960-2178
    DOI 10.1111/cea.14264
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review.

    Al-Hakim, Adam / Kacar, Mark / Savic, Sinisa

    Journal of clinical medicine

    2024  Volume 13, Issue 6

    Abstract: Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to ...

    Abstract Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID's relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients' heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.
    Language English
    Publishing date 2024-03-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm13061717
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Autoimmune and autoinflammatory manifestations in inborn errors of immunity.

    Kačar, Mark / Markelj, Gašper / Avčin, Tadej

    Current opinion in allergy and clinical immunology

    2022  Volume 22, Issue 6, Page(s) 343–351

    Abstract: Purpose of review: Autoimmune and inflammatory complications have been shown to arise in all age groups and across the spectrum of inborn errors of immunity (IEI). This review aims to highlight recent ground-breaking research and its impact on our ... ...

    Abstract Purpose of review: Autoimmune and inflammatory complications have been shown to arise in all age groups and across the spectrum of inborn errors of immunity (IEI). This review aims to highlight recent ground-breaking research and its impact on our understanding of IEI.
    Recent findings: Three registry-based studies of unprecedented size revealed the high prevalence of autoimmune, inflammatory and malignant complications in IEI. Two novel IEI were discovered: an autoinflammatory relopathy, cleavage-resistant RIPK1-induced autoinflammatory syndrome, as well as an inheritable phenocopy of PD-1 blockade-associated complication (as seen in cancer therapy) manifesting with multiorgan autoimmunity and Mycobacterium tuberculosis infection. A study examining patients with partial RAG deficiency pinpointed the specific defects leading to the failure of central and peripheral tolerance resulting in wide-ranging autoimmunity. A novel variant of Immunodeficiency Polyendocrinopathy Enteropathy X-linked syndrome was described, associated with preferential expression of a FOXP3 isoform lacking exon 2, linking exon-specific functions and the phenotypes corresponding to their absence. Lastly, we touch on recent findings pertaining actinopathies, the prototypical IEI with autoimmune, inflammatory and atopic complications.
    Summary: Dysregulated immunity has been associated with IEI since their discovery. Recently, large concerted efforts have shown how common these complications actually are while providing insight into normal and dysregulated molecular mechanisms, as well as describing novel diseases.
    MeSH term(s) Humans ; Autoimmunity ; Immunologic Deficiency Syndromes ; Registries ; Phenotype
    Language English
    Publishing date 2022-09-21
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2088710-3
    ISSN 1473-6322 ; 1528-4050
    ISSN (online) 1473-6322
    ISSN 1528-4050
    DOI 10.1097/ACI.0000000000000860
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Hemophagocytic Lymphohistiocytosis

    Kaçar, Ayşe Gonca / Celkan, Tiraje Tülin

    Balkan medical journal

    2022  Volume 39, Issue 5, Page(s) 309–317

    Abstract: ... immune response and a low number or absence of natural killer cells and cytotoxic T-lymphocytes are hallmarks ...

    Abstract Hemophagocytic lymphohistiocytosis (HLH) is an aggressive life-threatening disease that consists of uncontrolled activated lymphocytes and macrophages that secrete excessive cytokines. Symptoms and laboratory findings of HLH include prolonged fever, cytopenia, hepatosplenomegaly, liver dysfunction, hypertriglyceridemia, hyperferritinemia, increased soluble interleukin-2 receptor, low fibrinogen, and neurological problems. HLH has two forms: primary (familial autosomal recessive) or secondary (related to infections, malignancy, autoimmune and metabolic disorders, transplantations, chimeric antigen receptor T-cell therapies, etc.) form. As underlying conditions in HLH varied, clinical findings are nonspecific and disease diagnosis is challenging. Furthermore, patients diagnosed with primary HLH can have a secondary triggering agent, such as infection. Thus, there is no clear-cut distinction between these two forms. Abnormal immune response and a low number or absence of natural killer cells and cytotoxic T-lymphocytes are hallmarks of HLH. Despite the early and aggressive treatment, HLH is a deadly disease. Urgent immunosuppressive therapy is necessary to control hyperinflammation. Hematopoietic stem cell transplantation is a curative treatment in familial forms. Targeted therapy with emapalumab was also recently reported to be effective.
    MeSH term(s) Fever ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/pathology ; Lymphohistiocytosis, Hemophagocytic/therapy ; Splenomegaly
    Language English
    Publishing date 2022-08-15
    Publishing country Turkey
    Document type Journal Article
    ZDB-ID 2612982-6
    ISSN 2146-3131 ; 2146-3131
    ISSN (online) 2146-3131
    ISSN 2146-3131
    DOI 10.4274/balkanmedj.galenos.2022.2022-4-83
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The therapeutic effects of exosomes the first time isolated from pancreatic islet-derived progenitor cells in the treatment of pancreatic cancer.

    Hasoglu, Imren / Karatug Kacar, Ayse

    Protoplasma

    2023  Volume 261, Issue 2, Page(s) 281–291

    Abstract: ... of exosomes and the cell viability were detected. The cells were marked with HSP90, HSF-1, Kaspaz-8, Active ...

    Abstract Insulinoma is an excessive insulin-released beta cell tumor. Pancreas cancer is one of the deadliest malignant neoplasms. Exosomes are secreted cell membrane vesicles containing a large number of proteins, lipids, and nucleic acids. The aim of this study is to investigate the effects of exosomes on two cell lines of benign and malignant character. For the first time, exosomes were isolated from pancreatic island-derived progenitor cells (PID-PCs) and applied to INS-1 and MiaPaCa-2 cells. In addition, exosomes isolated from PID-PC, MiaPaca-2, and INS-1 cells were characterized in order to compare their sizes with other previously isolated exosomes. Alix, TSG101, CD9, and CD81 were analyzed. The size and concentration of exosomes and the cell viability were detected. The cells were marked with HSP90, HSF-1, Kaspaz-8, Active-Kaspaz-3, Beclin, and p-Bcl-2. The cell cytotoxicity and insulin levels kit were measured. Alix in all exosomes, and PID-PC, MiaPaca-2 cell lysates; TSG101 in PID-PC and MiaPaca-2 cell lysates; CD9 in INS-1 exosomes were detected. The dimensions of isolated exosomes were 103.6 ± 28.6 nm, 100.7 ± 10 nm, and 147.2 ± 12.3 nm for PID-PCs, MiaPaca-2, and INS-1 cells. The cell viability decreased and HSP90 increased in the MiaPaca-2 cells. The HSF-1 was higher in the control MiaPaca-2 cell compared to the control INS-1 cell, and the exosome-treated MiaPaca-2 cell compared to the exosome-treated INS-1 cell. Beclin and p-Bcl-2 were decreased in the exosome-treated MiaPaca-2 cells. The insulin level in the cell lysates increased compared to cell secretion in INS-1 cells. In conclusion, exosomes isolated from the PID-PC caused cell death in the MiaPaca-2 cells in a time- and dose-dependent manner. The IC50 value determined for MiaPaca-2 cells has no effect on cell viability in INS-1 cells, which best mimics pancreatic beta cells and can be used instead of healthy pancreatic beta cells. Isolated exosomes can kill cancer cells without damaging healthy cells.
    MeSH term(s) Humans ; Exosomes/metabolism ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Stem Cells/metabolism ; Stem Cells/pathology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Islets of Langerhans/metabolism ; Islets of Langerhans/pathology ; Insulins/metabolism
    Chemical Substances Proto-Oncogene Proteins c-bcl-2 ; Insulins
    Language English
    Publishing date 2023-10-06
    Publishing country Austria
    Document type Journal Article
    ZDB-ID 123809-7
    ISSN 1615-6102 ; 0033-183X
    ISSN (online) 1615-6102
    ISSN 0033-183X
    DOI 10.1007/s00709-023-01896-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Length of Hospital Stay and Survival of Hospitalized COVID-19 Patients During the Second Wave of the Pandemic: A Single Centre Retrospective Study from Slovenia.

    Rozman, Aleš / Rituper, Boštjan / Kačar, Mark / Kopač, Peter / Zidarn, Mihaela / Pohar Perme, Maja

    Zdravstveno varstvo

    2022  Volume 61, Issue 4, Page(s) 201–208

    Abstract: Background: As of writing, there are no publications pertaining to the prediction of COVID-19-related outcomes and length of stay in patients from Slovene hospitals.: Objectives: To evaluate the length of regular ward and ICU stays and assess the ... ...

    Abstract Background: As of writing, there are no publications pertaining to the prediction of COVID-19-related outcomes and length of stay in patients from Slovene hospitals.
    Objectives: To evaluate the length of regular ward and ICU stays and assess the survival of COVID-19 patients to develop better prediction models to forecast hospital capacity and staffing demands in possible further pandemic peaks.
    Methods: In this retrospective, single-site study we analysed the length of stay and survival of all patients, hospitalized due to the novel coronavirus (COVID-19) at the peak of the second wave, between November 18th 2020 and January 27th 2021 at the University Clinic Golnik, Slovenia.
    Results: Out of 407 included patients, 59% were male. The median length of stay on regular wards was 7.5 (IQR 5-13) days, and the median ICU length of stay was 6 (IQR 4-11) days. Age, male sex, and ICU stay were significantly associated with a higher risk of death. The probability of dying in 21 days at the regular ward was 14.4% (95% CI [10.9-18%]) and at the ICU it was 43.6% (95% CI [19.3-51.8%]).
    Conclusion: The survival of COVID-19 is strongly affected by age, sex, and the fact that a patient had to be admitted to ICU, while the length of hospital bed occupancy is very similar across different demographic groups. Knowing the length of stay and admission rate to ICU is important for proper planning of resources during an epidemic.
    Language English
    Publishing date 2022-09-28
    Publishing country Poland
    Document type Journal Article
    ISSN 0351-0026
    ISSN 0351-0026
    DOI 10.2478/sjph-2022-0027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Length of hospital stay and survival of hospitalized COVID-19 patients during the second wave of the pandemic

    Rozman Aleš / Rituper Boštjan / Kačar Mark / Kopač Peter / Zidarn Mihaela / Pohar Perme Maja

    Slovenian Journal of Public Health, Vol 61, Iss 4, Pp 201-

    A single centre retrospective study from Slovenia

    2022  Volume 208

    Abstract: As of writing, there are no publications pertaining to the prediction of COVID-19-related outcomes and length of stay in patients from Slovene hospitals. ...

    Abstract As of writing, there are no publications pertaining to the prediction of COVID-19-related outcomes and length of stay in patients from Slovene hospitals.
    Keywords covid-19 ; mortality ; length of stay ; intensive care units ; hospital wards ; umrljivost ; trajanje hospitalizacije ; intenzivni oddelki ; bolnišnični oddelki ; Public aspects of medicine ; RA1-1270
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher Sciendo
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Increased Focus on Internal Body Sensations Is Associated with Higher Patient-Perceived Severity of Allergic Rhinitis.

    Cvelbar Vozelj, Maja / Kačar, Mark / Bajec, Katarina Barbara / Šelb, Julij / Koren, Ana / Zidarn, Nuša / Korošec, Peter / Zidarn, Mihaela

    International archives of allergy and immunology

    2022  Volume 184, Issue 2, Page(s) 194–198

    Abstract: Background: Monitoring allergic rhinitis (AR) severity with objective biomarkers is important for the clinical management of patients as well as for research purposes. The most commonly used tool for the assessment of AR severity is the Total Nasal ... ...

    Abstract Background: Monitoring allergic rhinitis (AR) severity with objective biomarkers is important for the clinical management of patients as well as for research purposes. The most commonly used tool for the assessment of AR severity is the Total Nasal Symptom Score (TNSS). Objective biomarkers like skin prick test size or specific IgE levels do not correlate with TNSS.
    Objective: We hypothesize that the psychological factors are the missing link between patient-perceived severity of AR and objective biomarkers.
    Method: Thirty-nine patients (median age: 34 years; 21 [54%] female) with grass pollen-related AR were enrolled in our study. Patients allergic for perennial allergens and allergens with potentially overlapping seasons including cypress, ash/olive, plane, and nettle families were excluded. Patient-reported outcomes included symptom score, medication scores, combined score, and Juniper Mini Rhinitis Quality of Life Questionnaire (minRQLQ). Psychometric evaluation was performed using 5 different psychological questionnaires that measure 13 different psychological factors.
    Results: There was a significant correlation between the symptom score and private body consciousness (r = 0.50, p = 0.001) and neuroticism (R = 0.41 and p = 0.01). There was also a statistically significant correlation between the combined score and private body consciousness (r = 0.49 and p = 0.001) and with perceiving and understanding emotions (r = 0.34 and p = 0.04). The miniRQLQ score had a positive correlation with private body consciousness (r = 0.55 and p = 0.002) and observing (r = 0.42 and p = 0.02).
    Conclusions: Our data suggest that patients who are more aware of internal stimuli, as well as those who are highly self-conscious and somatically concerned tend to experience more severe AR symptoms.
    MeSH term(s) Humans ; Female ; Adult ; Male ; Rhinitis, Allergic, Seasonal/diagnosis ; Quality of Life ; Allergens ; Rhinitis, Allergic/diagnosis ; Biomarkers ; Sensation
    Chemical Substances Allergens ; Biomarkers
    Language English
    Publishing date 2022-11-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1108932-5
    ISSN 1423-0097 ; 1018-2438
    ISSN (online) 1423-0097
    ISSN 1018-2438
    DOI 10.1159/000527031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Hemophagocytic Lymphohistiocytosis

    Ayşe Gonca Kaçar / Tiraje Tülin Celkan

    Balkan Medical Journal, Vol 39, Iss 5, Pp 309-

    2022  Volume 317

    Abstract: ... immune response and a low number or absence of natural killer cells and cytotoxic T-lymphocytes are hallmarks ...

    Abstract Hemophagocytic lymphohistiocytosis (HLH) is an aggressive life-threatening disease that consists of uncontrolled activated lymphocytes and macrophages that secrete excessive cytokines. Symptoms and laboratory findings of HLH include prolonged fever, cytopenia, hepatosplenomegaly, liver dysfunction, hypertriglyceridemia, hyperferritinemia, increased soluble interleukin-2 receptor, low fibrinogen, and neurological problems. HLH has two forms: primary (familial autosomal recessive) or secondary (related to infections, malignancy, autoimmune and metabolic disorders, transplantations, chimeric antigen receptor T-cell therapies, etc.) form. As underlying conditions in HLH varied, clinical findings are nonspecific and disease diagnosis is challenging. Furthermore, patients diagnosed with primary HLH can have a secondary triggering agent, such as infection. Thus, there is no clear-cut distinction between these two forms. Abnormal immune response and a low number or absence of natural killer cells and cytotoxic T-lymphocytes are hallmarks of HLH. Despite the early and aggressive treatment, HLH is a deadly disease. Urgent immunosuppressive therapy is necessary to control hyperinflammation. Hematopoietic stem cell transplantation is a curative treatment in familial forms. Targeted therapy with emapalumab was also recently reported to be effective.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher Galenos Publishing House
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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