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  • 1
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    Online Resource
    SAT531 Thyroid Metastasis From Non-small Cell Lung Cancer: An Unusual Case Presentation
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. Supplement_1 ( 2023-10-05)
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: E.Y. Ibrahim: None. I. Guillen Alvarez: None. I. Hulinsky: None. D. Regelmann: None. C. Janowiecki: None. Background: Cases of thyroid tumors metastasizing from the lungs are rare, and their diagnosis is often challenging and can be mistaken for primary thyroid tumors or subacute thyroiditis. Thyroid function tests are typically normal and not helpful in establishing the diagnosis. Ultrasonography commonly shows focal or diffuse hypoechoic lesions. Correspondingly, heterogeneous hypodense areas with mild contrast enhancement are seen on CT scans. Clinical Case: Our patient is a 61-year-old male with a history of diabetes mellitus and 40 years tobacco use, who presented with a 1-week history of right-sided weakness and 3-weeks of dry cough. The weakness of his leg progressed to the point he could not ambulate. Initially, he was evaluated for a stroke and underwent CT imaging showing extensive lesions of the bilateral frontal, temporal, and parietal lobes. These findings were suspicious, and confirmed by MRI, to reflect multifocal metastatic lesions with vasogenic edema. Initial physical examination revealed a palpable thyroid nodule in the right lobe with bilateral cervical lymphadenopathy. CT of the neck demonstrated lymphadenopathy as well as multiple bilateral hypoechoic thyroid nodules, the largest of which measured 0.8 cm in the right thyroid lobe. TSH was 0.34 (0.48-4.17mU/L) with Free T4 at 1.39 (0.8-1.90ng/dL). The patient had denied symptoms of heat intolerance, tremor, or palpitations. A CT chest with contrast found a 3.5 cm cavitary lesion in the right upper lobe concerning for a primary lung neoplasm, as well as multiple bilateral lung nodules, mediastinal and hilar lymphadenopathy, and bilateral adrenal masses. Subsequent ultrasound-guided biopsy of the thyroid tumor revealed histologic features of a poorly differentiated non-small cell carcinoma, with features of a primary lung origin. These features were also present on a concurrent fine needle biopsy of an enlarged cervical lymph node. Immunohistochemistry staining showed the tumor was highly expressive for PDL1, focally positive for p40, pancytokeratin AE1/AE3, and negative for TTF-1 and thyroglobulinDue to the vasogenic cerebral edema, he was given dexamethasone with good response, and his weakness improved to the point that patient was able to ambulate. Treatment also included radiation therapy with subsequent pembrolizumab upon completion of radiotherapy. Conclusion: Several thyroid lesions representing metastases may go unnoticed because the physician’s attention toward lesions at other, more common sites, and detailed thyroid examination can be commonly overlooked. Patients with newly diagnosed malignancies should also be screened for thyroid involvement, including detailed physical, radiographic, and histologic examination of pathologic findings. Presentation Date: Saturday, June 17, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvad114.2002
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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  • 2
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    Online Resource
    Data_Sheet_2.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-4-29)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-4-29)
    Abstract: Purpose: This meta-analysis provides a longitudinal assessment of depression and cognitive impairment induced by taxane-based chemotherapy in women with breast cancer after 6 months of treatment. We highlighted the incidence and prevalence, the cognitive pattern in neuropsychological studies, and the relationship between chemotherapy-induced cognitive impairment and different risk factors. We estimated the effect sizes on each cognitive domain and differentiated effect sizes by each method of comparison of effects (i.e., baseline data, or control groups). Methods: The databases MEDLINE and Embase were searched for publications about taxane-related cognitive changes in patients with breast cancer published from 1980 to 2019. Cross-sectional and self-reported outcomes studies were excluded except for the depression item. Included studies were assessed for risk of bias with the Newcastle–Ottawa Scale. We estimated effect sizes for each cognitive domain and differentiated effect sizes by each method of comparison of effects. The review is reported in compliance with the PRISMA Statement; it was registered prospectively in PROSPERO as CRD42020163255. Results: Eleven studies meeting the criteria were analyzed, which resulted in a sample of 1,057 patients with breast cancer who received chemotherapy including 820 patients (77%) who received taxane-based chemotherapy. Attention and concentration, depression, and executive function domains had significant chemotherapy-induced impairment across all comparison types. Statistically significant improvement was found in language and verbal memory when comparing chemotherapy patients' test scores with baseline or matched controls. Taxane-based chemotherapy had a non-significant effect on processing speed, visual memory, visuospatial, and motor function domains. Conclusions: The occurrence of chemotherapy-induced cognitive impairment 6 months or more after the course of treatment in people with breast cancer is frequent in the domains of attention, executive function, and depression. Other domains appear stable or improve with time after treatment cessation.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.642382
    DOI: 10.3389/fonc.2021.642382.s001
    DOI: 10.3389/fonc.2021.642382.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 3
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    Online Resource
    Diagnostic Value of Preoperative Serum Calcitonin Levels in Medullary Thyroid Carcinoma
    Mary Ann Liebert Inc ; 2022
    In:  Clinical Thyroidology Vol. 34, No. 2 ( 2022-02-04), p. 85-88
    Details
    In: Clinical Thyroidology, Mary Ann Liebert Inc, Vol. 34, No. 2 ( 2022-02-04), p. 85-88
    Type of Medium: Online Resource
    ISSN: 2329-9711 , 2329-972X
    URL: Article
    DOI: 10.1089/ct.2022;34.85-88
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2022
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  • 4
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    Online Resource
    Treatment and surveillance of advanced, metastatic iodine-resistant differentiated thyroid cancer
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Current Opinion in Oncology Vol. 29, No. 2 ( 2017-03), p. 151-158
    Details
    In: Current Opinion in Oncology, Ovid Technologies (Wolters Kluwer Health), Vol. 29, No. 2 ( 2017-03), p. 151-158
    Abstract: This review will focus on the management and treatment of metastatic thyroid cancer that is radioactive iodine refractory and review the new drugs and their mechanism of actions as well as their adverse events. Recent findings Until recently, there were no efficacious therapeutic modalities for these patients. With advancement in knowledge and research of the molecular aberrations and oncogenic mutations in thyroid cancer as well as further understanding the role of angiogenesis in tumor growth molecular pathogenesis, novel targeted therapies are available for these patients. Some of these drugs have successfully prolonged progression free survival and are now Food and Drug Administration approved. Additional agents are approved for the treatment of other types of cancers and are currently under investigation for differentiated thyroid cancer treatment. Summary Differentiated thyroid cancer (papillary and follicular) is the most common endocrine malignancy. It is generally known to have an excellent prognosis and patients are usually cured with the conventional primary treatments including surgery, radioactive iodine, and thyroid stimulating hormone suppression. A minor proportion of patients do not fully recover mainly because they develop radioactive iodine-resistant disease. These patients have few treatment options, which we aimed to describe here.
    Type of Medium: Online Resource
    ISSN: 1040-8746 , 1531-703X
    URL: Article
    DOI: 10.1097/CCO.0000000000000349
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2026986-9
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  • 5
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    Online Resource
    Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer
    American Association for Cancer Research (AACR) ; 2022
    In:  Clinical Cancer Research Vol. 28, No. 12 ( 2022-06-13), p. 2587-2597
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 28, No. 12 ( 2022-06-13), p. 2587-2597
    Abstract: We examined gene expression, germline variant, and somatic mutation features associated with pathologic response to neoadjuvant durvalumab plus chemotherapy in basal-like triple-negative breast cancer (bTNBC). Experimental Design: Germline and somatic whole-exome DNA and RNA sequencing, programmed death ligand 1 (PD-L1) IHC, and stromal tumor-infiltrating lymphocyte scoring were performed on 57 patients. We validated our results using 162 patients from the GeparNuevo randomized trial. Results: Gene set enrichment analysis showed that pathways involved in immunity (adaptive, humoral, innate), JAK–STAT signaling, cancer drivers, cell cycle, apoptosis, and DNA repair were enriched in cases with pathologic complete response (pCR), whereas epithelial–mesenchymal transition, extracellular matrix, and TGFβ pathways were enriched in cases with residual disease (RD). Immune-rich bTNBC with RD was enriched in CCL-3, -4, -5, -8, -23, CXCL-1, -3, -6, -10, and IL1, -23, -27, -34, and had higher expression of macrophage markers compared with immune-rich cancers with pCR that were enriched in IFNγ, IL2, -12, -21, chemokines CXCL-9, -13, CXCR5, and activated T- and B-cell markers (GZMB, CD79A). In the validation cohort, an immune-rich five-gene signature showed higher expression in pCR cases in the durvalumab arm (P = 0.040) but not in the placebo arm (P = 0.923) or in immune-poor cancers. Independent of immune markers, tumor mutation burden was higher, and PI3K, DNA damage repair, MAPK, and WNT/β-catenin signaling pathways were enriched in germline and somatic mutations in cases with pCR. Conclusions: The TGFβ pathway is associated with immune-poor phenotype and RD in bTNBC. Among immune-rich bTNBC RD, macrophage/neutrophil chemoattractants dominate the cytokine milieu, and IFNγ and activated B cells and T cells dominate immune-rich cancers with pCR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-21-3215
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 6
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    Online Resource
    Hope, Cure, and Adverse Effects in Immunotherapy: Atezolizumab-Associated Encephalitis in Metastatic Small Cell Lung Cancer – A Case Report and Literature Review
    S. Karger AG ; 2022
    In:  Case Reports in Neurology Vol. 14, No. 3 ( 2022-9-20), p. 366-371
    Details
    In: Case Reports in Neurology, S. Karger AG, Vol. 14, No. 3 ( 2022-9-20), p. 366-371
    Abstract: Cancer immunotherapies have been revolutionary treatments in oncological disease. Such therapies include immune checkpoint inhibitors that target programmed cell death protein, ligands, and cytotoxic T-lymphocyte-associated antigen (CTLA-4). Increased use has led to recognition of immune-related adverse events. Such events are often distinct from the typical adverse events of traditional cancer therapies. Immune-related adverse events are more commonly found to affect the skin, gastrointestinal tract, and endocrine system. The incidence of these adverse events remains low for central nervous system effects. This article describes a case of atezolizumab-associated encephalitis in a patient with metastatic small cell lung cancer.
    Type of Medium: Online Resource
    ISSN: 1662-680X
    URL: Article
    DOI: 10.1159/000526248
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 2505302-4
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  • 7
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    Online Resource
    Characterization of the tumor immune microenvironment of triple-negative breast cancer (TNBC) patients who self-identify as African American (AA) or non-African American (NonAA).
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 564-564
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 564-564
    Abstract: 564 Background: What tumor biological differences, if any, contribute to the higher incidence and worse prognosis of triple negative breast cancer (TNBC) in African American (AA) compared to NonAA patients are unknown. We hypothesized that differences in the tumor immune microenvironment may contribute to the outcome disparities. The purpose of this study was to characterize and compare the immune microenvironment of TNBC between patients self-identified as NonAA or AA. Methods: Formalin fixed paraffin embedded surgically resected cancer and paired normal tissues collected before any systemic therapy and the corresponding clinical data were collected for NonAA (n = 56) and AA (n = 54) stage I-III TNBC treated at Yale Cancer Center between 2000-2017. The two cohorts were matched for clinical stage, age of diagnosis, and year of diagnosis. We performed somatic and germline whole exome sequencing (WES), bulk RNA sequencing, and immunohistochemistry to assess PD-L1 expression (SP142). Stromal tumor infiltrating lymphocytes (sTILs) were assessed on H & E slides. Mutation load, mutation frequencies, and gene expression differences were compared at gene and pathway level. Immune cell composition was estimated through gene expression deconvolution analyses (TIDE). Results: Tumor mutational burden was similar between the two cohorts. At gene level, few genes had significantly different somatic mutation frequencies, or differential mRNA expression between AA and NonAA samples. Pathway level alterations showed inflammation, immunity (adaptive; innate), antigen presentation, and allograft rejection pathways were more affected by somatic mutations in AA samples. The affected genes differed from cancer to cancer and were not recurrent and therefore were missed at gene level analysis. Gene set enrichment and co-expression analysis also showed higher immune related pathway expression in AA samples. Unsupervised co-expression cluster analysis confirmed coordinated overexpression of genes involved in immunity, inflammation, and cytokine/chemokine signaling in AA patients. Two immunotherapy response predictive signatures, immune inflamed and the IFNG as well as sTILs score and PD-L1 positivity were also higher in AA samples. These findings raise the possibility that immune checkpoint inhibitors might be particularly effective in AA patients. In NonAA samples, the EMT transition, angiogenesis, adipogenesis, myogenesis, fatty acid metabolism, TGFβ signaling, UV-response, and hypoxia pathways were overexpressed. TIDE analysis suggested higher levels of TAM M2, overall TIDE score, and the Immune Exclusion score in NonAA samples. Conclusions: TNBC in AA patients more frequently harbor somatic mutations in genes involved with immune functions and overexpress immune and inflammatory genes compared to NonAA patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.564
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Online Resource
    FRI331 Autoimmune Hypophysitis Secondary To Ipilimumab And Nivolumab Combination Therapy In A Patient With Advanced Renal Cell Carcinoma
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. Supplement_1 ( 2023-10-05)
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: E.Y. Ibrahim: None. I. Hulinsky: None. D. Regelmann: None. Introduction: Ipilimumab and nivolumab combination therapy is an effective immune checkpoint inhibitor regimen indicated for advanced stages of renal cell carcinoma. Autoimmune hypophysitis is a rare adverse event from this therapy that occurs in only 3-6% of patients. The mechanism underlying immune checkpoint inhibitor-induced hypophysitis is not fully understood but involves immune, inflammatory, and genetic factors. Clinical Case: A 65-year-old male with a history of hypertension and type 2 diabetes mellitus, recently diagnosed with renal cell carcinoma with metastasis to the lungs presents to the emergency department with three days of generalized weakness and worsening confusion, accompanied by 2 weeks of headache. Two months prior to presentation, the patient began chemotherapy with four cycles of nivolumab and ipilimumab. The emergency department team initiated a stroke code for right facial droop and right-sided weakness seen on his physical exam. The CT of the patient’s head was unremarkable. The patient was also hypotensive (BP 90/40 mmHg) and tachycardic (140 bpm). He received 3 liters of crystalloid as well as diltiazem injection without improvement. Random cortisol on admission at 11:00 am was 1 ug/dl (3.4-22), ACTH was 7 pg/mL (6-50), Na was 135 mEq/L (137 - 145) and K was 5.1 mEq/L (3.5 - 5.0). Furthermore, TSH 0.02 μIU/ml (0.47-4.70), ILGF 39 ng/mL (41-279), and total testosterone levels & lt;3 ng/dL (139-740) were low. The free thyroxine level was measured at 1.00 ng/dL (0.8-1.9), and MRI revealed a normal sella tursica. Based on these findings, we diagnosed the patient with hypopituitarism, likely due to hypophysitis as an immune-related adverse event of immune checkpoint inhibitor therapy. Consequently, we discontinued the administration of Ipilimumab-Nivolumab combination therapy and started oral dexamethasone 8 mg and fludrocortisone 0.1 mg for mineralocorticoid supplementation. The patient’s symptoms resolved, and laboratory data showed improvements in hyponatremia, hyperkalemia, and hypoglycemia. The care team transitioned the patient’s steroid regimen to prednisone 25 mg daily maintenance dose, and the patient was discharged with stress dosing instructions. Conclusion: Diagnosis of hypophysitis as an immune-related adverse event is challenging due to its vague presentation. However, a delayed diagnosis can be life-threatening. As a result, clinicians must maintain a high index of suspicion for presentations of weakness and headache in consistent clinical contexts, in order to provide optimal management and minimize morbidity. Additionally, early management of hypophysitis can reduce the interval of immune checkpoint inhibitor therapy, which in turn affects the course of cancer. Presentation: Friday, June 16, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvad114.1266
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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  • 9
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    Online Resource
    A preliminary, prospective study of peripheral neuropathy and cognitive function in patients with breast cancer during taxane therapy
    Public Library of Science (PLoS) ; 2022
    In:  PLOS ONE Vol. 17, No. 10 ( 2022-10-7), p. e0275648-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 10 ( 2022-10-7), p. e0275648-
    Abstract: Dramatic improvements in cancer survival have occurred in the last decade, but the quality of life for many survivors is compromised due to severe, long-lasting, and often irreversible side effects of chemotherapy. The neurological side effects, chemotherapy induced peripheral neuropathy (CIPN) and cancer related/induced cognitive impairment (CRCI/CICI), are under-recognized and can occur after chemotherapy, immunotherapy, or radiation. The cellular mechanisms underlying these neurological side effects are poorly understood and there are no effective treatments or preventions, other than reduction or termination of cancer therapy. In our preliminary prospective, non-interventional study to examine the side effects of chemotherapy in patients with breast cancer (NCT03872141), patients with breast cancer who received standard of care single agent weekly taxane-based chemotherapy were assessed at baseline, midpoint, and end of treatment for neurological and cognitive changes and for blood levels of potential protein biomarkers (n = 13). CIPN and CRCI both showed an increase in severity with accumulating taxane and these changes were compared to protein alternations over the course of treatment. Using peripheral blood collected from patients (n = 10) during chemotherapy and tested with an antibody array curated by the MD Anderson RPPA Core), we found that 19 proteins were increased, and 12 proteins decreased over 12 weeks of treatment. Among those downregulate were proteins known to be critical for neuronal viability and function including GRB2 (growth factor receptor-bound protein 2) and NCS1 (neuronal calcium sensor 1). Concurrently, proteins associated with apoptosis, including BAK1 (Bcl-1 homologous antagonist/killer), were upregulated. These results support the proposal that CIPN and CRCI increase with increasing taxane exposure, and identified several proteins that are altered with taxane exposure that could be implicated in their pathogenesis. In conclusion, our study provides evidence for progressive neurological changes and the rationale to investigate the molecular basis for these changes with the goal of target identification for mitigation of these neurological side effects.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
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    DOI: 10.1371/journal.pone.0275648
    DOI: 10.1371/journal.pone.0275648.g001
    DOI: 10.1371/journal.pone.0275648.g002
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    DOI: 10.1371/journal.pone.0275648.g005
    DOI: 10.1371/journal.pone.0275648.t001
    DOI: 10.1371/journal.pone.0275648.t002
    DOI: 10.1371/journal.pone.0275648.s001
    DOI: 10.1371/journal.pone.0275648.s002
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    DOI: 10.1371/journal.pone.0275648.s006
    DOI: 10.1371/journal.pone.0275648.s007
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2022
    detail.hit.zdb_id: 2267670-3
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  • 10
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    Online Resource
    Role of Thermal Ablation for Papillary Thyroid Microcarcinomas: A Systematic Review
    Mary Ann Liebert Inc ; 2023
    In:  Clinical Thyroidology Vol. 35, No. 6 ( 2023-06-01), p. 242-245
    Details
    In: Clinical Thyroidology, Mary Ann Liebert Inc, Vol. 35, No. 6 ( 2023-06-01), p. 242-245
    Type of Medium: Online Resource
    ISSN: 2329-9711 , 2329-972X
    URL: Article
    DOI: 10.1089/ct.2023;35.242-245
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2023
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