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  1. Article ; Online: TP53

    Pan, Minggui / Jiang, Chen / Zhang, Zheyang / Achacoso, Ninah / Alexeeff, Stacey / Solorzano, Aleyda V / Tse, Pam / Chung, Elaine / Sundaresan, Tilak / Suga, Jennifer Marie / Thomas, Sachdev / Habel, Laurel A

    JCO precision oncology

    2023  Volume 7, Page(s) e2200570

    Abstract: Purpose: To examine the impact of : Methods: This cohort included patients with locally advanced, recurrent, and de novo metastatic PDAC with next-generation sequencing performed from November 2017 to May 2022. We defined R175H, R248W, R248Q, R249S, ... ...

    Abstract Purpose: To examine the impact of
    Methods: This cohort included patients with locally advanced, recurrent, and de novo metastatic PDAC with next-generation sequencing performed from November 2017 to May 2022. We defined R175H, R248W, R248Q, R249S, R273H, R273L, and R282W as GOF and all other p53 mutations (mutp53) as non-GOF. We used Cox regression modeling to examine the association between GOF and non-GOF mutp53 and overall survival (OS), adjusting for demographics, performance status, Charlson comorbidity index, receipt of chemotherapy, and
    Results: Of 893 total eligible patients, 68.5% had tumors with mutp53, 90.1% had
    Conclusion: GOF and non-GOF mutp53 were associated with differential prognosis in advanced PDAC. The adverse effect of mutKRAS on OS appeared to be primarily driven by patients with mutCDKN2A. Our results provide new insight that could be helpful for prognostic stratification in clinical practice and for aiding future clinical trial designs.
    MeSH term(s) Humans ; Tumor Suppressor Protein p53/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/genetics ; Prognosis ; Adenocarcinoma/genetics ; Mutation/genetics ; Pancreatic Neoplasms
    Chemical Substances Tumor Suppressor Protein p53 ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; TP53 protein, human
    Language English
    Publishing date 2023-05-10
    Publishing country United States
    Document type Journal Article
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.22.00570
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Sex- and Co-Mutation-Dependent Prognosis in Patients with SMARCA4-Mutated Malignancies.

    Pan, Minggui / Jiang, Chen / Zhang, Zheyang / Achacoso, Ninah / Solorzano-Pinto, Aleyda V / Tse, Pam / Chung, Elaine / Suga, Jennifer Marie / Thomas, Sachdev / Habel, Laurel A

    Cancers

    2023  Volume 15, Issue 10

    Abstract: Background: Whether sex and co-mutations impact prognosis of patients with SMARCA4-mutated (mutSMARCA4) malignancies is not clear.: Methods: This cohort included patients from Northern California Kaiser Permanente with next-generation sequencing (NGS) ...

    Abstract Background: Whether sex and co-mutations impact prognosis of patients with SMARCA4-mutated (mutSMARCA4) malignancies is not clear.
    Methods: This cohort included patients from Northern California Kaiser Permanente with next-generation sequencing (NGS) performed from August 2020 to October 2022. We used Cox regression modeling to examine the association between sex and overall survival (OS), adjusting for demographics, performance status, Charlson comorbidity index, receipt of treatment, tumor mutation burden (TMB), and
    Results: Out of 9221 cases with NGS performed, 125 cases (1.4%) had a mutSMARCA4. The most common malignancies with a mutSMARCA4 were non-small cell lung cancer (NSCLC, 35.2%), esophageal and stomach adenocarcinoma (12.8%), and cancer of unknown primary (11.2%). The most common co-mutations were
    Conclusion: In our cohort of patients with mutSMARCA4, males had substantially worse prognosis than females, while mutTP53, mutKRAS, mutCDKN2A, mutSTK11 and mutKeap1were differentially associated with prognosis among all patients and among the NSCLC subgroup. Our results, if confirmed, could suggest potentially unidentified mechanisms that underly this sex and co-mutation-dependent prognostic disparity among patients whose tumor bears a mutSMARCA4.
    Language English
    Publishing date 2023-05-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15102665
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  3. Article ; Online: Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer.

    Chen, Lujia / Wang, Ying / Cai, Chunhui / Ding, Ying / Kim, Rim S / Lipchik, Corey / Gavin, Patrick G / Yothers, Greg / Allegra, Carmen J / Petrelli, Nicholas J / Suga, Jennifer Marie / Hopkins, Judith O / Saito, Naoyuki G / Evans, Terry / Jujjavarapu, Srinivas / Wolmark, Norman / Lucas, Peter C / Paik, Soonmyung / Sun, Min /
    Pogue-Geile, Katherine L / Lu, Xinghua

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2024  Volume 42, Issue 13, Page(s) 1520–1530

    Abstract: Purpose: A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who ...

    Abstract Purpose: A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects.
    Methods: We trained a new machine learning model, referred to as the colon oxaliplatin signature (COLOXIS) model, for predicting response to oxaliplatin-containing regimens. We examined whether COLOXIS was predictive of oxaliplatin benefits in the CC adjuvant setting among 1,065 patients treated with 5-fluorouracil plus leucovorin (FULV; n = 421) or FULV + oxaliplatin (FOLFOX; n = 644) from NSABP C-07 and C-08 phase III trials. The COLOXIS model dichotomizes patients into COLOXIS+ (oxaliplatin responder) and COLOXIS- (nonresponder) groups. Eight-year recurrence-free survival was used to evaluate oxaliplatin benefits within each of the groups, and the predictive value of the COLOXIS model was assessed using the
    Results: Among 1,065 patients, 526 were predicted as COLOXIS+ and 539 as COLOXIS-. The COLOXIS+ prediction was associated with prognosis for FULV-treated patients (hazard ratio [HR], 1.52 [95% CI, 1.07 to 2.15];
    Conclusion: The COLOXIS model is predictive of oxaliplatin benefits in the CC adjuvant setting. The results provide evidence supporting a change in CC adjuvant therapy: reserve oxaliplatin only for COLOXIS+ patients, but further investigation is warranted.
    MeSH term(s) Humans ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/pathology ; Colonic Neoplasms/mortality ; Machine Learning ; Oxaliplatin/therapeutic use ; Oxaliplatin/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Fluorouracil/therapeutic use ; Fluorouracil/administration & dosage ; Leucovorin/therapeutic use ; Leucovorin/administration & dosage ; Male ; Female ; Middle Aged ; Aged ; Organoplatinum Compounds/therapeutic use ; Organoplatinum Compounds/administration & dosage ; Chemotherapy, Adjuvant ; Adult ; Clinical Trials, Phase III as Topic ; Neoplasm Staging
    Chemical Substances Oxaliplatin (04ZR38536J) ; Fluorouracil (U3P01618RT) ; Leucovorin (Q573I9DVLP) ; Organoplatinum Compounds
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.23.01080
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    Zs.A 1847: Show issues Location:
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  4. Article ; Online: TP53

    Pan, Minggui / Jiang, Chen / Tse, Pam / Achacoso, Ninah / Alexeeff, Stacey / Solorzano, Aleyda V / Chung, Elaine / Hu, Wenwei / Truong, Thach-Giao / Arora, Amit / Sundaresan, Tilak / Suga, Jennifer Marie / Thomas, Sachdev / Habel, Laurel A

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2021  Volume 40, Issue 2, Page(s) 171–179

    Abstract: Purpose: To examine the association of gain-of-function (GOF) and non-gain-of-function (non-GOF) : Methods: This cohort study included patients with metastatic colorectal cancer (CRC) who had next-generation sequencing performed from November 2017 to ...

    Abstract Purpose: To examine the association of gain-of-function (GOF) and non-gain-of-function (non-GOF)
    Methods: This cohort study included patients with metastatic colorectal cancer (CRC) who had next-generation sequencing performed from November 2017 to January 2021. We defined R175H, R248W, R248Q, R249S, R273H, R273L, and R282W as GOF and all other mutp53 as non-GOF. We used Cox regression modeling to examine the association between GOF and non-GOF mutp53 and overall survival (OS), adjusting for age, sex, ethnicity, performance status, Charlson comorbidity index and receipt of chemotherapy.
    Results: Of total 1,043 patients, 735 had tumors with mutp53 and 308 had wild-type p53 (wtp53). GOF was associated with worse OS than non-GOF mutp53 only in LCC (hazard ratio [HR] = 1.66 [95% CI, 1.20 to 2.29]), but not in RCC (HR = 0.79 [95% CI, 0.49 to 1.26]). Importantly, RCC was associated with worse OS than LCC only in the subset of patients whose CRC carried non-GOF (HR = 1.76 [95% CI, 1.30 to 2.39]), but not GOF mutp53 (HR = 0.92 [95% CI, 0.55 to 1.53]) or wtp53 (HR = 0.88 [95% CI, 0.60 to 1.28]). These associations were largely unchanged after also adjusting for RAS, BRAF, and PIK3CA mutations, and microsatellite instability-high.
    Conclusion: Poorer survival of patients with metastatic RCC versus LCC appeared to be restricted to the subset with non-GOF mutp53, whereas GOF versus non-GOF mutp53 was associated with poorer survival only among patients with LCC. This approach of collectively classifying mutp53 into GOF and non-GOF provides new insight for prognostic stratification and for understanding the mechanism of sidedness-dependent prognosis. If confirmed, future CRC clinical trials may benefit from incorporating this approach.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; California ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; DNA Mutational Analysis ; Databases, Factual ; Female ; Gain of Function Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Suppressor Protein p53/genetics ; Young Adult
    Chemical Substances Biomarkers, Tumor ; TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2021-11-29
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.21.02014
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  5. Article ; Online: S1417CD: A Prospective Multicenter Cooperative Group-Led Study of Financial Hardship in Metastatic Colorectal Cancer Patients.

    Shankaran, Veena / Unger, Joseph M / Darke, Amy K / Suga, Jennifer Marie / Wade, James L / Kourlas, Peter J / Chandana, Sreenivasa R / O'Rourke, Mark A / Satti, Suma / Liggett, Diane / Hershman, Dawn L / Ramsey, Scott D

    Journal of the National Cancer Institute

    2021  Volume 114, Issue 3, Page(s) 372–380

    Abstract: Background: Financial toxicity is a growing problem in oncology, but no prior studies have prospectively measured the financial impact of cancer treatment in a diverse national cohort of newly diagnosed cancer patients. S1417CD was the first cooperative ...

    Abstract Background: Financial toxicity is a growing problem in oncology, but no prior studies have prospectively measured the financial impact of cancer treatment in a diverse national cohort of newly diagnosed cancer patients. S1417CD was the first cooperative group-led multicenter prospective cohort study to evaluate financial hardship in metastatic colorectal cancer (mCRC) patients.
    Methods: Patients aged 18 years or older within 120 days of mCRC diagnosis completed quarterly questionnaires for 12 months. We estimated the cumulative incidence of major financial hardship (MFH), defined as 1 or more of increased debt, new loans from family and/or friends, selling or refinancing home, or 20% or more income decline. We evaluated the association between patient characteristics and MFH using multivariate cox regression and the association between MFH and quality of life using linear regression.
    Results: A total of 380 patients (median age = 59.9 years) were enrolled; 77.7% were White, 98.0% insured, and 56.5% had annual income of $50 000 or less. Cumulative incidence of MFH at 12 months was 71.3% (95% confidence interval = 65.7% to 76.1%). Age, race, marital status, and income (split at $50 000 per year) were not statistically significantly associated with MFH. However, income less than $100 000 and total assets less than $100 000 were both associated with greater MFH. MFH at 3 months was associated with decreased social functioning and quality of life at 6 months.
    Conclusions: Nearly 3 out of 4 mCRC patients experienced MFH despite access to health insurance. These findings underscore the need for clinic and policy solutions that protect cancer patients from financial harm.
    MeSH term(s) Adolescent ; Colonic Neoplasms ; Cost of Illness ; Financial Stress ; Humans ; Income ; Middle Aged ; Prospective Studies ; Quality of Life
    Language English
    Publishing date 2021-12-29
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2992-0
    ISSN 1460-2105 ; 0027-8874 ; 0198-0157
    ISSN (online) 1460-2105
    ISSN 0027-8874 ; 0198-0157
    DOI 10.1093/jnci/djab210
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  6. Article ; Online: Examining the role of access to care: Racial/ethnic differences in receipt of resection for early-stage non-small cell lung cancer among integrated system members and non-members.

    Check, Devon K / Albers, Kathleen B / Uppal, Kanti M / Suga, Jennifer Marie / Adams, Alyce S / Habel, Laurel A / Quesenberry, Charles P / Sakoda, Lori C

    Lung cancer (Amsterdam, Netherlands)

    2018  Volume 125, Page(s) 51–56

    Abstract: Objectives: To examine the role of uniform access to care in reducing racial/ethnic disparities in receipt of resection for early stage non-small cell lung cancer (NSCLC) by comparing integrated health system member patients to demographically similar ... ...

    Abstract Objectives: To examine the role of uniform access to care in reducing racial/ethnic disparities in receipt of resection for early stage non-small cell lung cancer (NSCLC) by comparing integrated health system member patients to demographically similar non-member patients.
    Materials and methods: Using data from the California Cancer Registry, we conducted a retrospective cohort study of patients from four racial/ethnic groups (White, Black, Hispanic, Asian/Pacific Islander), aged 21-80, with a first primary diagnosis of stage I or II NSCLC between 2004 and 2011, in counties served by Kaiser Permanente Northern California (KPNC) at diagnosis. Our cohort included 1565 KPNC member and 4221 non-member patients. To examine the relationship between race/ethnicity and receipt of surgery stratified by KPNC membership, we used modified Poisson regression to calculate risk ratios (RR) adjusted for patient demographic and tumor characteristics.
    Results: Black patients were least likely to receive surgery regardless of access to integrated care (64-65% in both groups). The magnitude of the black-white difference in the likelihood of surgery receipt was similar for members (RR: 0.82, 95% CI: 0.73-0.93) and non-members (RR: 0.86, 95% CI: 0.80-0.94). Among members, roughly equal proportions of Hispanic and White patients received surgery; however, among non-members, Hispanic patients were less likely to receive surgery (non-members, RR: 0.93, 95% CI: 0.86-1.00; members, RR: 0.98, 95% CI: 0.89-1.08).
    Conclusion: Disparities in surgical treatment for NSCLC were not reduced through integrated health system membership, suggesting that factors other than access to care (e.g., patient-provider communication) may underlie disparities. Future research should focus on identifying such modifiable factors.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; California ; Carcinoma, Non-Small-Cell Lung/surgery ; Female ; Health Services Accessibility/ethics ; Healthcare Disparities/ethics ; Humans ; Lung Neoplasms/surgery ; Male ; Middle Aged ; Population Groups/ethics ; Retrospective Studies ; Young Adult
    Language English
    Publishing date 2018-09-11
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 632771-0
    ISSN 1872-8332 ; 0169-5002
    ISSN (online) 1872-8332
    ISSN 0169-5002
    DOI 10.1016/j.lungcan.2018.09.006
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  7. Article ; Online: Racial disparities on the use of invasive and noninvasive staging in patients with non-small cell lung cancer.

    Suga, Jennifer Marie / Nguyen, Danh V / Mohammed, Sandra M / Brown, Monica / Calhoun, Royce / Yoneda, Ken / Gandara, David R / Lara, Primo N

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

    2010  Volume 5, Issue 11, Page(s) 1772–1778

    Abstract: Introduction: Racial disparities have been reported in non-small cell lung cancer (NSCLC) staging and therapeutic outcomes. We investigated whether such disparities exist in the era of modern noninvasive staging modalities, including positron emission ... ...

    Abstract Introduction: Racial disparities have been reported in non-small cell lung cancer (NSCLC) staging and therapeutic outcomes. We investigated whether such disparities exist in the era of modern noninvasive staging modalities, including positron emission tomography scan use.
    Methods: NSCLC patients from the California Cancer Registry diagnosed between January 1, 1994, and December 31, 2004, were included. The likelihood of obtaining invasive (thoracoscopy, bronchoscopy, and mediastinoscopy) and noninvasive staging procedures (computed tomography, magnetic resonance imaging, and positron emission tomography scans), along with surgical resection, were analyzed using logistic regression adjusted for known confounders.
    Results: Of 13,762 NSCLC patients, 12,395 with adequate staging information were included. 10,217 patients (82%) were classified as white, 2178 patients (18%) were non-white, and 738 were black patients (6%). No association was seen between race and the use of either noninvasive (odds ratio [OR] = 1.02; p = 0.76) or invasive staging procedures (OR = 0.96; p = 0.44). However, compared with white patients, black patients had a lower likelihood of undergoing surgery, regardless of noninvasive (OR = 0.6; p <0.001) or invasive staging use (OR = 0.63; p = 0.02). There was no survival difference for those who underwent surgery between white and non-white patients, regardless of noninvasive (hazard ratio = 0.95; p = 0.45) or invasive staging (hazard ratio = 1.03; p = 0.79).
    Conclusions: In contrast to prior published work, we found no difference in rates of both invasive and noninvasive staging between white and non-white patients. However, non-white patients-particularly blacks-were less likely to receive surgery. The reason for the apparent difference in surgical rates could not be explained by the variables we evaluated. Thus, other factors such as personal preference or access to care require further investigation.
    MeSH term(s) Adult ; African Continental Ancestry Group/statistics & numerical data ; Aged ; Aged, 80 and over ; California ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging ; Carcinoma, Non-Small-Cell Lung/ethnology ; Carcinoma, Non-Small-Cell Lung/pathology ; Cohort Studies ; European Continental Ancestry Group/statistics & numerical data ; Female ; Healthcare Disparities/ethnology ; Humans ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/ethnology ; Lung Neoplasms/pathology ; Magnetic Resonance Imaging ; Male ; Mediastinoscopy ; Middle Aged ; Neoplasm Staging/instrumentation ; Neoplasm Staging/methods ; Positron-Emission Tomography ; Prognosis ; Thoracoscopy ; Tomography, X-Ray Computed ; Young Adult
    Language English
    Publishing date 2010-11
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2432037-7
    ISSN 1556-1380 ; 1556-0864
    ISSN (online) 1556-1380
    ISSN 1556-0864
    DOI 10.1097/JTO.0b013e3181f69f22
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