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Article ; Online: Frontiers in Soft Tissue Tumor Pathology.

Charville, Gregory W

Surgical pathology clinics

2023 Volume 17, Issue 1, Page(s) ix

Language	English
Publishing date	2023-07-28
Publishing country	United States
Document type	Editorial
ISSN	1875-9157
ISSN (online)	1875-9157
DOI	10.1016/j.path.2023.07.005
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Article: Contemporary diagnostic approach to atypical vascular lesion and angiosarcoma.

Rutland, Cooper D / Bean, Gregory R / Charville, Gregory W

Seminars in diagnostic pathology

2023 Volume 40, Issue 4, Page(s) 284–294

Abstract: Vascular neoplasms account for a substantial fraction of cutaneous mesenchymal tumors, spanning from clinically indolent benign lesions to highly aggressive malignancies. These neoplasms present a distinctive challenge in terms of their diagnostic ... ...

Abstract	Vascular neoplasms account for a substantial fraction of cutaneous mesenchymal tumors, spanning from clinically indolent benign lesions to highly aggressive malignancies. These neoplasms present a distinctive challenge in terms of their diagnostic histopathology, both because of the breadth of their morphological manifestations and because of the significant histological overlap between different entities, even benign and malignant ones. The post-radiotherapy setting is particularly problematic diagnostically, insofar as radiation exposure predisposes not only to secondary angiosarcoma, but also to atypical vascular lesion, a largely benign proliferation of cutaneous blood vessels typically affecting the breast. To address these challenges, we explore the clinical, histological, and molecular features of malignant vascular neoplasia, including primary and secondary subtypes, through the comparative lens of atypical vascular lesion. In addition to highlighting the key morphological indicators of malignancy in superficial vasoformative tumors, we offer an approach that integrates clinical characteristics and molecular genetic profiling to facilitate accurate classification. With this current knowledge as our foundation, we also look ahead in an effort to frame some of the key unanswered questions regarding superficial vascular malignancies and their natural history, clinical management, and molecular underpinnings.
MeSH term(s)	Humans ; Female ; Hemangiosarcoma/diagnosis ; Hemangiosarcoma/genetics ; Vascular Neoplasms/diagnosis ; Vascular Neoplasms/complications ; Vascular Neoplasms/pathology ; Neoplasms, Radiation-Induced/diagnosis ; Neoplasms, Radiation-Induced/genetics ; Neoplasms, Radiation-Induced/complications ; Skin Neoplasms/diagnosis ; Skin Neoplasms/genetics ; Breast/pathology ; Breast Neoplasms/pathology
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605834-6
ISSN	1930-1111 ; 0740-2570
ISSN (online)	1930-1111
ISSN	0740-2570
DOI	10.1053/j.semdp.2023.04.017
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Zs.A 1988: Show issues

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Article: Diagnosis of soft tissue tumors using immunohistochemistry as a surrogate for recurrent fusion oncoproteins.

Black, Margaret A / Charville, Gregory W

Seminars in diagnostic pathology

2021 Volume 39, Issue 1, Page(s) 38–47

Abstract: Soft tissue neoplasms encompass a broad spectrum of clinicopathologic manifestations. In a subset of soft tissue tumors, spanning a wide range of clinical behavior from indolent to highly aggressive, recurrent genetic translocations yield oncogenic ... ...

Abstract	Soft tissue neoplasms encompass a broad spectrum of clinicopathologic manifestations. In a subset of soft tissue tumors, spanning a wide range of clinical behavior from indolent to highly aggressive, recurrent genetic translocations yield oncogenic fusion proteins that drive neoplastic growth. Beyond functioning as primary mechanisms of tumorigenesis, recurrent translocations represent key diagnostic features insofar as the presence of a particular oncogenic gene fusion generally points to specific tumor entities. In addition to more direct methods for identifying recurrent translocations, such as conventional cytogenetics or fluorescence in situ hybridization, immunohistochemistry for a component of the fusion oncoprotein increasingly is being used as a surrogate marker, exploiting the tendency of these fusion components to be distinctively overexpressed by translocation-bearing tumor cells. Diagnostic immunohistochemistry can also be used to identify the characteristic gene expression changes that occur downstream of oncogenic fusions. Here, we review the use of immunohistochemistry to detect surrogate markers of recurrent translocations in soft tissue tumors, focusing on the practical applications and limitations of this diagnostic approach.
MeSH term(s)	Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Oncogene Proteins ; Soft Tissue Neoplasms/genetics
Chemical Substances	Oncogene Proteins
Language	English
Publishing date	2021-11-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605834-6
ISSN	1930-1111 ; 0740-2570
ISSN (online)	1930-1111
ISSN	0740-2570
DOI	10.1053/j.semdp.2021.10.005
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Article ; Online: CDX2 expression in malignant peripheral nerve sheath tumour: a potential diagnostic pitfall associated with PRC2 inactivation.

Odeyemi, Olumide O / Ozawa, Michael G / Charville, Gregory W

Histopathology

2022 Volume 80, Issue 6, Page(s) 995–1000

Abstract: Aims: Malignant peripheral nerve sheath tumour (MPNST) is a soft tissue sarcoma that exhibits features of Schwann cell differentiation. Heterologous, often mesenchymal-type differentiation occurs in a subset of MPNST, while glandular morphology also is ... ...

Abstract	Aims: Malignant peripheral nerve sheath tumour (MPNST) is a soft tissue sarcoma that exhibits features of Schwann cell differentiation. Heterologous, often mesenchymal-type differentiation occurs in a subset of MPNST, while glandular morphology also is encountered in rare cases. We observed in MPNST unanticipated expression of CDX2, a transcription factor that regulates intestinal epithelial differentiation, and aimed to further characterize this phenomenon. Methods/results: Expression of CDX2 was assessed by immunohistochemistry in a total of 32 high-grade MPNSTs lacking morphological evidence of epithelial differentiation, including twelve tumours (38%) that developed in the setting of neurofibromatosis and four (13%) in the setting of prior radiation therapy. CDX2 was expressed by 14 of 32 MPNSTs (44%), wherein immunoreactivity, varying from weak to strong, was present in 2-95% of neoplastic spindle cells (median 10%, mean 23%). Notably, CDX2 expression was limited to tumours with PRC2 inactivation (22/32; 69%), as evidenced immunohistochemically by diffuse loss of trimethylated histone H3K27. Analysing publicly available RNA-sequencing data from twelve MPNST cell lines, two of which are clonally related, we observed CDX2 expression in all six PRC2-inactivated cell lines, while CDX2 expression was negligible in six cell lines with intact PRC2, amounting to a 58-fold increase in CDX2 expression on average with PRC2 inactivation. Conclusions: CDX2 is expressed in a subset of MPNSTs, even in the absence of morphological evidence of epithelial differentiation. CDX2 expression in MPNST is strongly associated with underlying PRC2 inactivation.
MeSH term(s)	Biomarkers, Tumor/analysis ; CDX2 Transcription Factor/metabolism ; DNA Methylation ; Histones/metabolism ; Humans ; Nerve Sheath Neoplasms/diagnosis ; Neurilemmoma/diagnosis ; Neurilemmoma/pathology ; Neurofibrosarcoma/pathology
Chemical Substances	Biomarkers, Tumor ; CDX2 Transcription Factor ; CDX2 protein, human ; Histones
Language	English
Publishing date	2022-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14626
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Article ; Online: CHRNA6 RNA In Situ Hybridization Is a Useful Tool for the Diagnosis of Extraskeletal Myxoid Chondrosarcoma.

Dulken, Ben W / Kingsley, Leandra / Zdravkovic, Sabrina / Cespedes, Oscar / Qian, Xiaohua / Suster, David I / Charville, Gregory W

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2024 Volume 37, Issue 5, Page(s) 100464

Abstract: Extraskeletal myxoid chondrosarcoma (EMC) is an uncommon mesenchymal neoplasm characteristically composed of uniform-appearing round to spindle-shaped cells with eosinophilic cytoplasm and abundant myxoid extracellular matrix. Although the majority of ... ...

Abstract	Extraskeletal myxoid chondrosarcoma (EMC) is an uncommon mesenchymal neoplasm characteristically composed of uniform-appearing round to spindle-shaped cells with eosinophilic cytoplasm and abundant myxoid extracellular matrix. Although the majority of cases harbor a pathognomonic t(9;22) translocation that fuses EWSR1 with the orphan nuclear receptor NR4A3, there are less common variants that partner NR4A3 with TAF15, TCF12, or TFG. By immunohistochemistry, EMC has features of both cartilaginous and neuroendocrine differentiation, as evidenced by inconsistent expression of S100 protein and synaptophysin or INSM1, respectively, in a subset of cases. Given the limitations of available immunohistochemical stains for the diagnosis of EMC, we analyzed genome-wide gene expression microarray data to identify candidate biomarkers based on differential expression in EMC in comparison with other mesenchymal neoplasms. This analysis pointed to CHRNA6 as the gene with the highest relative expression in EMC (96-fold; P = 8.2 × 10
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2024.100464
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Article ; Online: Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy.

Zhou, Maggie Y / Bui, Nam Q / Charville, Gregory W / Ganjoo, Kristen N / Pan, Minggui

International journal of molecular sciences

2023 Volume 24, Issue 11

Abstract: Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options remain limited. WDLPS and DDLPS both exhibit the characteristic amplification of ... ...

Abstract	Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options remain limited. WDLPS and DDLPS both exhibit the characteristic amplification of chromosome region 12q13-15, which contains the genes
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors ; Liposarcoma/genetics ; Liposarcoma/therapy ; Liposarcoma/pathology ; Immunotherapy ; Docetaxel ; Doxorubicin ; Proto-Oncogene Proteins c-mdm2/genetics
Chemical Substances	Immune Checkpoint Inhibitors ; Docetaxel (15H5577CQD) ; Doxorubicin (80168379AG) ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27)
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24119571
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Article ; Online: Diagnosing liposarcoma on (peri)-renal mass biopsy: A clinicopathological study of 30 cases.

Potterveld, Susan K / Mubeen, Aysha / Anderson, William J / Clay, Michael R / Bourgeau, Melanie / Charville, Gregory W / Sangoi, Ankur R

Histopathology

2024

Abstract: Aims: Classification of renal neoplasms on small tissue biopsies is in increasing demand, and maintaining broad differential diagnostic considerations in this setting is necessary. When evaluating a renal or perirenal tumour biopsy with sarcomatoid ... ...

Abstract	Aims: Classification of renal neoplasms on small tissue biopsies is in increasing demand, and maintaining broad differential diagnostic considerations in this setting is necessary. When evaluating a renal or perirenal tumour biopsy with sarcomatoid morphology, together with sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma as top diagnostic considerations, it is vital to additionally consider the possibility of well-differentiated and de-differentiated liposarcoma. Methods and results: This study reports a series of 30 biopsy samples from sites in or around the kidney collected from four institutions in which the correct diagnosis was either well-differentiated or de-differentiated liposarcoma. The majority (26 of 30, 87%) of lesions were accurately diagnosed on biopsy sampling, all of which incorporated testing for MDM2 by immunohistochemistry (IHC), fluorescence in-situ hybridisation (FISH) or a combination of the two as part of the diagnostic work-up. Tumour expression of MDM2 by IHC without confirmatory FISH analysis was sometimes (30%) sufficient to reach a diagnosis, but demonstration of MDM2 amplification by FISH was ascertained in the majority (57%) of biopsy samples. A diagnosis of de-differentiated liposarcoma was not definitively established until resection in four (13%) patients, as no MDM2 testing was performed on the corresponding pre-operative biopsies. Conclusions: When a retroperitoneal tumour is not clinically suspected, histological consideration of a liposarcoma diagnosis may be overlooked. Implementation of ancillary immunohistochemical and cytogenetic testing can ultimately lead to a definitive diagnosis in this potentially misleading anatomical location.
Language	English
Publishing date	2024-04-22
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15197
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Article ; Online: Management Strategies and Outcomes in Primary Liver Angiosarcoma.

Ramakrishnan, Neeraj / Mokhtari, Ryan / Charville, Gregory W / Bui, Nam / Ganjoo, Kristen

American journal of clinical oncology

2023 Volume 46, Issue 10, Page(s) 439–444

Abstract: Objectives: Primary hepatic angiosarcoma is a rare tumor of the liver that originates from endothelial and fibroblastic tissue, with poor prognosis and lack of standardized treatment. We retrospectively analyzed the clinical characteristics and ... ...

Abstract	Objectives: Primary hepatic angiosarcoma is a rare tumor of the liver that originates from endothelial and fibroblastic tissue, with poor prognosis and lack of standardized treatment. We retrospectively analyzed the clinical characteristics and treatment outcomes of 23 patients with primary liver angiosarcoma treated at an academic sarcoma center. Methods: We screened all patients with primary liver angiosarcoma treated at Stanford between 2000 and 2022. Data was collected from EPIC electronic medical records and included patient demographics, tumor characteristics, treatment modalities, and patient outcomes. Statistical analysis was completed using Python 3.0, while survival curves were generated using the Kaplan-Meier method and Lifelines Packages. Results: There were nearly equal numbers of males (11) and females (12) in our study, with most patients aged 70 to 79 at diagnosis. The median overall survival (OS) was 6 months (range 0.07 to 222.6 mo). The 2- and 5-year OS were both 38.6%. 71% of patients received systemic treatment with chemotherapy, while 29% received immunotherapy. Local treatment with surgery or radioembolization was performed in 14% of patients. Three patients in our study displayed particularly improved OS and received various treatments, which ranged from hepatic resection to ipilimumab/nivolumab. Conclusion: Our study demonstrated that primary liver angiosarcoma has poor outcomes despite treatment. Surgical resection with negative margins is the only curative modality. However, most patients present with advanced disease and are not surgical candidates. Further research is needed to identify more effective systemic therapy options for this devastating disease.
MeSH term(s)	Male ; Female ; Humans ; Hemangiosarcoma/therapy ; Hemangiosarcoma/pathology ; Prognosis ; Retrospective Studies ; Liver Neoplasms/therapy ; Liver Neoplasms/pathology
Language	English
Publishing date	2023-08-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	604536-4
ISSN	1537-453X ; 0277-3732
ISSN (online)	1537-453X
ISSN	0277-3732
DOI	10.1097/COC.0000000000001032
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Article ; Online: The abundance and morphology of human large intestinal goblet and tuft cells during chronic schistosomiasis.

Gologorsky, Matthew B / Mechler, Claire M / Forgó, Erna / Charville, Gregory W / Howitt, Michael R

Parasite immunology

2023 Volume 45, Issue 6, Page(s) e12981

Abstract: Schistosomiasis affects nearly 240 million people in predominately low- and middle-income countries and ranks second in the number of cases and socio-economic burden among all parasitic diseases. Despite the enormous burden posed by schistosomes, our ... ...

Abstract	Schistosomiasis affects nearly 240 million people in predominately low- and middle-income countries and ranks second in the number of cases and socio-economic burden among all parasitic diseases. Despite the enormous burden posed by schistosomes, our understanding of how schistosomiasis impacts infected human tissues remains limited. Intestinal schistosomiasis in animal models leads to goblet cell hyperplasia, likely increasing mucus production and reflecting an intestinal type 2 immune response. However, it is unknown whether these same changes occur in schistosome-infected humans. Using immunofluorescence and light microscopy, we compared the abundance and morphology of goblet cells in patients diagnosed with schistosomiasis to uninfected controls. The mucin-containing vesicles in goblet cells from schistosome-infected patients were significantly larger (hypertrophic) than uninfected individuals, although goblet cell hyperplasia was absent in chronic human schistosomiasis. In addition, we examined tuft cells in the large intestinal epithelium of control and schistosome-infected patients. Tuft cell numbers expand during helminth infection in mice, but these cells have not been characterized in human parasite infections. We found no evidence of tuft cell hyperplasia during human schistosome infection. Thus, our study provides novel insight into schistosome-associated changes to the intestinal epithelium in humans, suggesting an increase in mucus production by large intestinal goblet cells but relatively minor effects on tuft cell numbers.
MeSH term(s)	Humans ; Animals ; Mice ; Hyperplasia/metabolism ; Hyperplasia/pathology ; Schistosomiasis ; Goblet Cells/metabolism ; Intestinal Mucosa/metabolism ; Mucins/metabolism
Chemical Substances	Mucins
Language	English
Publishing date	2023-04-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	424444-8
ISSN	1365-3024 ; 0141-9838
ISSN (online)	1365-3024
ISSN	0141-9838
DOI	10.1111/pim.12981
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Article: The Majority of Patients Who Undergo ERCP When Large Duct Obstruction Is Evident on Liver Biopsy Have Biliary Findings Amenable to Endoscopic Intervention.

Martin, Melissa / Lee, Justin / Gugig, Roberto / Ofosu, Andrew / Charville, Gregory W / Barakat, Monique T

Journal of clinical medicine

2023 Volume 12, Issue 2

Abstract: 1) Background: Abnormal liver function tests are commonly encountered in clinical practice, often leading to additional workup to determine the underlying etiology of these abnormal laboratory studies. As part of this evaluation, if less invasive ... ...

Abstract	(1) Background: Abnormal liver function tests are commonly encountered in clinical practice, often leading to additional workup to determine the underlying etiology of these abnormal laboratory studies. As part of this evaluation, if less invasive imaging studies are performed and are without evidence of biliary obstruction, liver biopsy may be performed, and the finding of large duct obstruction on liver biopsy is commonly encountered. The utility of endoscopic retrograde cholangiopancreatography (ERCP) for evaluation and management of possible biliary obstruction in patients with large duct obstruction on liver biopsy has not been studied to date. (2) Methods: To assess the utility of ERCP in patients with large bile duct obstruction on liver biopsy, we retrospectively evaluated patients with large duct obstruction on liver biopsy from 2010-2019 at our tertiary care and transplant center. Demographic and clinical characteristics were evaluated for all patients, with sub-group analysis for patients who underwent ERCP and those who had intervenable findings at the time of ERCP. Descriptive statistics with proportions, means, and standard deviations were performed for demographics and clinical variables using absolute standardized difference. (3) Results: During the study period, 189 liver biopsies with evidence of large duct obstruction were performed. After exclusion criteria were applied, 166 unique patients were eligible for the study. Ninety-one patients with evidence of large duct obstruction on liver biopsy underwent ERCP and 75 did not. Of the 91 patients who underwent ERCP, 76 patients (84%) had an intervenable finding at ERCP. Patients who underwent ERCP were overall more likely to have had a liver transplant (65% ASD 0.63), have previously undergone cholecystectomy (80%, ASD 0.56), and be immunocompromised (80%, ASD 0.56). (4) Conclusions: ERCP is high yield when large duct obstruction is apparent on liver biopsy, with the majority of patients (84%) who undergo ERCP in this clinical context having a biliary finding necessitating therapeutic endoscopic intervention.
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12020482
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