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Article ; Online: Single-Cell RNA-Seq Identifies Pathways and Genes Contributing to the Hyperandrogenemia Associated with Polycystic Ovary Syndrome.

Harris, R Alan / McAllister, Jan M / Strauss, Jerome F

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenemia of ovarian thecal cell origin, resulting in anovulation/oligo-ovulation and infertility. Our previous studies established that ovarian theca cells isolated ...

Abstract	Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenemia of ovarian thecal cell origin, resulting in anovulation/oligo-ovulation and infertility. Our previous studies established that ovarian theca cells isolated and propagated from ovaries of normal ovulatory women and women with PCOS have distinctive molecular and cellular signatures that underlie the increased androgen biosynthesis in PCOS. To evaluate differences between gene expression in single-cells from passaged cultures of theca cells from ovaries of normal ovulatory women and women with PCOS, we performed single-cell RNA sequencing (scRNA-seq). Results from these studies revealed differentially expressed pathways and genes involved in the acquisition of cholesterol, the precursor of steroid hormones, and steroidogenesis. Bulk RNA-seq and microarray studies confirmed the theca cell differential gene expression profiles. The expression profiles appear to be directed largely by increased levels or activity of the transcription factors SREBF1, which regulates genes involved in cholesterol acquisition (
MeSH term(s)	Female ; Humans ; Polycystic Ovary Syndrome/metabolism ; Single-Cell Gene Expression Analysis ; Hyperandrogenism/complications ; Hyperandrogenism/genetics ; Hyperandrogenism/metabolism ; Transcription Factors/genetics
Chemical Substances	Transcription Factors
Language	English
Publishing date	2023-06-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310611
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Article ; Online: Bilateral intracortical inhibition during unilateral motor preparation and sequence learning.

Hamel, R / Waltzing, B M / Hinder, M R / McAllister, C J / Jenkinson, N / Galea, J M

Brain stimulation

2024 Volume 17, Issue 2, Page(s) 349–361

Abstract: Motor sequence learning gradually quickens reaction time, suggesting that sequence learning alters motor preparation processes. Interestingly, evidence has shown that preparing sequence movements decreases short intracortical inhibition (SICI) in the ... ...

Abstract	Motor sequence learning gradually quickens reaction time, suggesting that sequence learning alters motor preparation processes. Interestingly, evidence has shown that preparing sequence movements decreases short intracortical inhibition (SICI) in the contralateral motor cortex (M1), but also that sequence learning alters motor preparation processes in both the contralateral and ipsilateral M1s. Therefore, one possibility is that sequence learning alters the SICI decreases occurring during motor preparation in bilateral M1s. To examine this, two novel hypotheses were tested: unilateral sequence preparation would decrease SICI in bilateral M1s, and sequence learning would alter such bilateral SICI responses. Paired-pulse transcranial magnetic stimulation was delivered over the contralateral and ipsilateral M1s to assess SICI in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. In the absence of sequence learning, SICI decreased in both the contralateral and ipsilateral M1s during the preparation of sequences initiated by the right index finger, suggesting that SICI decreases in bilateral M1s during unilateral motor preparation. As sequence learning progressed, SICI decreased in the contralateral M1 whilst it increased in the ipsilateral M1. Moreover, these bilateral SICI responses were observed at the onset of motor preparation, suggesting that sequence learning altered baseline SICI levels rather than the SICI decreases occurring during motor preparation per se. Altogether, these results suggest that SICI responses in bilateral M1s reflect two motor processes: an acute decrease of inhibition during motor preparation, and a cooperative but bidirectional shift of baseline inhibition levels as sequence learning progresses.
Language	English
Publishing date	2024-03-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2394410-9
ISSN	1876-4754 ; 1935-861X
ISSN (online)	1876-4754
ISSN	1935-861X
DOI	10.1016/j.brs.2024.03.009
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Article ; Online: Population ecology and juvenile density hotspots of thornback ray (Raja clavata) around the Shetland Islands, Scotland.

McAllister, Mia / Fraser, Shaun / Henry, Lea-Anne

Journal of fish biology

2023 Volume 104, Issue 3, Page(s) 576–589

Abstract: ... Scotland, was investigated in two habitats: inshore (50-150 m deep) and shallow coastal (20-50 m deep ... Fish Survey, the size composition of R. clavata catches was compared between shallow and inshore ... of R. clavata was significantly higher in shallow than that in inshore areas (ANOVA, F = 72.52, df = 1 ...

Abstract	Elasmobranchs are facing global decline, and so there is a pressing need for research into their populations to inform effective conservation and management strategies. Little information exists on the population ecology of skate species around the British Isles, presenting an important knowledge gap that this study aimed to reduce. The population ecology of thornback ray (Raja clavata) around the Shetland Islands, Scotland, was investigated in two habitats: inshore (50-150 m deep) and shallow coastal (20-50 m deep), from 2011 to 2022, and 2017 to 2022, respectively. Using trawl survey data from the annual Shetland Inshore Fish Survey, the size composition of R. clavata catches was compared between shallow and inshore habitats across 157 trawl sets, and 885 individuals, over the years 2017-2022. Catch per unit effort (CPUE) of R. clavata was significantly higher in shallow than that in inshore areas (ANOVA, F = 72.52, df = 1, 5, p < 0.001). Size composition also significantly differed between the two habitats (analysis of similarities, R = 0.96, p = 0.002), with R. clavata being smaller in shallow areas and juveniles (<60 cm) occurring more frequently. Spatial distribution maps confirmed density hotspots of juveniles in shallow habitats, with repeated use of certain locations consistent over time. The results of this study provide the first evidence for R. clavata using shallow areas for potential nurseries in Shetland, which can inform the IUCN's Important Shark and Ray Area process. Furthermore, this study provides important new population ecology information for R. clavata around Shetland, which may have important conservation implications and be valuable for informing species and fisheries stock assessments in this region.
MeSH term(s)	Animals ; Skates, Fish ; Ecology ; United Kingdom ; Scotland ; Ecosystem ; Fisheries
Language	English
Publishing date	2023-11-20
Publishing country	England
Document type	Journal Article
ZDB-ID	410564-3
ISSN	1095-8649 ; 0022-1112
ISSN (online)	1095-8649
ISSN	0022-1112
DOI	10.1111/jfb.15610
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Article ; Online: Translation, cross-cultural adaptation, and preliminary validation of a patient-reported outcome measure for genetic counseling outcomes in Sweden.

Pestoff, Rebecka / Danielsson, Henrik / McAllister, Marion / Johansson, Peter / Gunnarsson, Cecilia

Journal of genetic counseling

2024

Abstract: Genetic counseling is key for understanding the consequences of hereditary and genetic diseases and, therefore, crucial for patients, their families, and healthcare providers. Genetic counseling facilitates individuals' comprehension, decision-making, ... ...

Abstract	Genetic counseling is key for understanding the consequences of hereditary and genetic diseases and, therefore, crucial for patients, their families, and healthcare providers. Genetic counseling facilitates individuals' comprehension, decision-making, and adaptation to hereditary diseases. This study focuses on the Swedish adaptation of the Genetic Counseling Outcome Scale-24 (GCOS-24), an internationally validated, patient-reported outcome measure (PROM) for quantifying patient empowerment in genetic counseling. This study aimed to translate and cross-culturally adapt the GCOS-24 to measure patient-reported outcome from genetic counseling in Sweden. The adaptation process was meticulously conducted, adhering to international guidelines, with cross-cultural adaptation, translation, and back translation, to ensure semantic, conceptual, and idiomatic equivalence with the original English version. Face validity and understandability was assured using qualitative cognitive interviews conducted with patient representatives, and by a committee of experts in the field. The psychometric properties of the Swedish version of GCOS-24 (GCOS-24swe) were evaluated using a robust sample of 374 patients. These individuals received genetic counseling by telephone or video, necessitated by the constraints of the COVID-19 pandemic. Participants responded to GCOS-24swe both before and after genetic counseling. The GCOS-24swe demonstrated face validity, good internal consistency (Cronbach's alpha = 0.86), significant responsiveness (Cohen's d = 0.65, p < 0.001), and good construct validity. The study's findings underscore the GCOS-24swe's potential as an effective instrument in both clinical practice and research within Sweden. It offers a valuable means for assessing patient empowerment, a key goal of genetic counseling. Additional psychometric assessment of test-retest reliability and interpretability would further enhance the utility of GCOS-24swe.
Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1117799-8
ISSN	1573-3599 ; 1059-7700
ISSN (online)	1573-3599
ISSN	1059-7700
DOI	10.1002/jgc4.1896
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Article ; Online: Spectral Flow Cytometry Methods and Pipelines for Comprehensive Immunoprofiling of Human Peripheral Blood and Bone Marrow.

Spasic, Milos / Ogayo, Esther R / Parsons, Adrienne M / Mittendorf, Elizabeth A / van Galen, Peter / McAllister, Sandra S

Cancer research communications

2024 Volume 4, Issue 3, Page(s) 895–910

Abstract: Profiling hematopoietic and immune cells provides important information about disease risk, disease status, and therapeutic responses. Spectral flow cytometry enables high-dimensional single-cell evaluation of large cohorts in a high-throughput manner. ... ...

Abstract	Profiling hematopoietic and immune cells provides important information about disease risk, disease status, and therapeutic responses. Spectral flow cytometry enables high-dimensional single-cell evaluation of large cohorts in a high-throughput manner. Here, we designed, optimized, and implemented new methods for deep immunophenotyping of human peripheral blood and bone marrow by spectral flow cytometry. Two blood antibody panels capture 48 cell-surface markers to assess more than 58 cell phenotypes, including subsets of T cells, B cells, monocytes, natural killer (NK) cells, and dendritic cells, and their respective markers of exhaustion, activation, and differentiation in less than 2 mL of blood. A bone marrow antibody panel captures 32 markers for 35 cell phenotypes, including stem/progenitor populations, T-cell subsets, dendritic cells, NK cells, and myeloid cells in a single tube. We adapted and developed innovative flow cytometric analysis algorithms, originally developed for single-cell genomics, to improve data integration and visualization. We also highlight technical considerations for users to ensure data fidelity. Our protocol and analysis pipeline accurately identifies rare cell types, discerns differences in cell abundance and phenotype across donors, and shows concordant immune landscape trends in patients with known hematologic malignancy. Significance: This study introduces optimized methods and analysis algorithms that enhance capabilities in comprehensive immunophenotyping of human blood and bone marrow using spectral flow cytometry. This approach facilitates detection of rare cell types, enables measurement of cell variations across donors, and provides proof-of-concept in identifying known hematologic malignancies. By unlocking complexities of hematopoietic and immune landscapes at the single-cell level, this advancement holds potential for understanding disease states and therapeutic responses.
MeSH term(s)	Humans ; Bone Marrow ; Flow Cytometry/methods ; Monocytes ; Myeloid Cells ; Immunophenotyping
Language	English
Publishing date	2024-03-11
Publishing country	United States
Document type	Journal Article
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-23-0357
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Article ; Online: A Postoperative Nausea and Vomiting Update: Current information on New Drugs, Old Drugs, Rescue/Treatment, Combination Therapies and Nontraditional Modalities.

Meyer, Tricia A / Hutson, Larry R / Morris, Phillip M / McAllister, Russell K

Advances in anesthesia

2023 Volume 41, Issue 1, Page(s) 17–38

Abstract: This article's objective is to present the latest evidence and information on the management of postoperative nausea and vomiting (PONV). PONV continues to affect 30% of the surgical population causing patient dissatisfaction, extending length of stay, ... ...

Abstract	This article's objective is to present the latest evidence and information on the management of postoperative nausea and vomiting (PONV). PONV continues to affect 30% of the surgical population causing patient dissatisfaction, extending length of stay, and increasing overall costs. This review includes the introduction of 2 new intravenous formulations of antiemetics (amisulpride, aprepitant), updates on nontraditional therapies, suggestions for combination prophylaxis, emerging data on rescue treatment, and considerations for special populations and settings. Both of the new antiemetics provide promising options for pharmacologic interventions for PONV with favorable safety profiles.
MeSH term(s)	Humans ; Postoperative Nausea and Vomiting/drug therapy ; Postoperative Nausea and Vomiting/prevention & control ; Antiemetics/therapeutic use ; Combined Modality Therapy ; Aprepitant ; Administration, Intravenous
Chemical Substances	Antiemetics ; Aprepitant (1NF15YR6UY)
Language	English
Publishing date	2023-07-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632613-4
ISSN	1878-0415 ; 0737-6146
ISSN (online)	1878-0415
ISSN	0737-6146
DOI	10.1016/j.aan.2023.05.002
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Article: Round Goby (

McAllister, Keith / Drake, D Andrew R / Power, Michael

Biological invasions

2022 Volume 24, Issue 9, Page(s) 2885–2903

Abstract: Numerous fish species in the Laurentian Great Lakes have been negatively impacted by the establishment of the invasive Round Goby ( ...

Abstract	Numerous fish species in the Laurentian Great Lakes have been negatively impacted by the establishment of the invasive Round Goby (
Language	English
Publishing date	2022-05-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1438729-3
ISSN	1573-1464 ; 1387-3547
ISSN (online)	1573-1464
ISSN	1387-3547
DOI	10.1007/s10530-022-02816-4
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Article ; Online: The experiences of families receiving a diagnosis of 22q11.2 deletion syndrome in Ireland.

O'Donoghue, Emma / McAllister, Marion / Rizzo, Roberta

Journal of genetic counseling

2022 Volume 32, Issue 3, Page(s) 618–634

Abstract: Families in Ireland often wait over 1 year to see a genetic counselor (GC). This qualitative study aimed to explore the views of families who received a diagnosis of 22q11DS in Ireland regarding the need for timely access to genetic counseling at the ... ...

Abstract	Families in Ireland often wait over 1 year to see a genetic counselor (GC). This qualitative study aimed to explore the views of families who received a diagnosis of 22q11DS in Ireland regarding the need for timely access to genetic counseling at the point of diagnosis. Twenty participants were recruited through the '22q Ireland' support group, giving a response rate of approximately 10% of the total support group members. Semi-structured interviews were conducted online and by telephone which explored experiences of receiving diagnoses, medical care, genetic counseling, mental health, and coping with the diagnosis. Interviews were transcribed verbatim and analyzed using thematic analysis. The experiences of 20 participants were classified into five main themes: Receiving Diagnosis, Interactions with Healthcare Professionals (HCPs, excluding GCs), Medical Care, Information, and Impact of Condition. Participants reported receiving diagnoses for their children in a sub-optimal manner due to inappropriate settings and insufficient information, support, and pre-test counseling. Parents reported feeling responsible for managing their child's complex and fragmented medical care. Participants reported insufficient empathy and little awareness of 22q11DS among HCPs. Participants perceived genetic counseling to be associated with family planning and reported delayed, if any, access to services. Mental health was a particular worry among participants. Conferences about 22q11DS are the main source of information for parents. Participants reported a range of emotions after diagnosis and described the family impact. The findings suggest both an association between HCPs' poor understanding of 22q11DS and the perceived lack of empathy from HCPs and fragmented medical care. There is an identified need for advocacy of the GC profession in Ireland to support these families. Increased awareness of 22q11DS among HCPs and the development of a coordinated care pathway for 22q11DS, with timely access to genetic counseling, may improve care and lead to better outcomes.
MeSH term(s)	Child ; Humans ; DiGeorge Syndrome/psychology ; Ireland ; Parents/psychology ; Adaptation, Psychological ; Qualitative Research
Language	English
Publishing date	2022-12-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1117799-8
ISSN	1573-3599 ; 1059-7700
ISSN (online)	1573-3599
ISSN	1059-7700
DOI	10.1002/jgc4.1667
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Article ; Online: Single-Cell RNA-Seq Identifies Pathways and Genes Contributing to the Hyperandrogenemia Associated with Polycystic Ovary Syndrome

R. Alan Harris / Jan M. McAllister / Jerome F. Strauss

International Journal of Molecular Sciences, Vol 24, Iss 10611, p

2023 Volume 10611

Abstract	Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenemia of ovarian thecal cell origin, resulting in anovulation/oligo-ovulation and infertility. Our previous studies established that ovarian theca cells isolated and propagated from ovaries of normal ovulatory women and women with PCOS have distinctive molecular and cellular signatures that underlie the increased androgen biosynthesis in PCOS. To evaluate differences between gene expression in single-cells from passaged cultures of theca cells from ovaries of normal ovulatory women and women with PCOS, we performed single-cell RNA sequencing (scRNA-seq). Results from these studies revealed differentially expressed pathways and genes involved in the acquisition of cholesterol, the precursor of steroid hormones, and steroidogenesis. Bulk RNA-seq and microarray studies confirmed the theca cell differential gene expression profiles. The expression profiles appear to be directed largely by increased levels or activity of the transcription factors SREBF1, which regulates genes involved in cholesterol acquisition ( LDLR , LIPA , NPC1 , CYP11A1 , FDX1 , and FDXR ), and GATA6, which regulates expression of genes encoding steroidogenic enzymes ( CYP17A1 ) in concert with other differentially expressed transcription factors ( SP1 , NR5A2 ). This study provides insights into the molecular mechanisms underlying the hyperandrogenemia associated with PCOS and highlights potential targets for molecular diagnosis and therapeutic intervention.
Keywords	polycystic ovary syndrome ; single-cell RNA sequencing ; human ovarian theca cells ; androgens ; steroids ; cholesterol ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Complete anatomic segmentectomy shows improved oncologic outcomes compared to incomplete anatomic segmentectomy.

McAllister, Miles A / Rochefort, Matthew M / Ugalde Figueroa, Paula / Leo, Rachel / Sugarbaker, Evert A / Singh, Anupama / Herrera-Zamora, Julio / Barcelos, Rafael R / Mazzola, Emanuele / Heiling, Hillary / Jaklitsch, Michael T / Bueno, Raphael / Swanson, Scott J

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2024 Volume 65, Issue 3

Abstract: Objectives: To compare oncologic outcomes after segmentectomy with division of segmental bronchus, artery and vein (complete anatomic segmentectomy) versus segmentectomy with division of <3 segmental structures (incomplete anatomic segmentectomy).: ... ...

Abstract	Objectives: To compare oncologic outcomes after segmentectomy with division of segmental bronchus, artery and vein (complete anatomic segmentectomy) versus segmentectomy with division of <3 segmental structures (incomplete anatomic segmentectomy). Methods: We conducted a single-centre, retrospective analysis of patients undergoing segmentectomy from March 2005 to May 2020. Operative reports were audited to classify procedures as complete or incomplete anatomic segmentectomy. Patients who underwent neoadjuvant therapy or pulmonary resection beyond indicated segments were excluded. Survival was estimated with Kaplan-Meier models and compared using log-rank tests. Cox proportional hazards models were used to estimate hazard ratios (HRs) for death. Cumulative incidence functions for loco-regional recurrence were compared with Gray's test, with death considered a competing event. Cox and Fine-Gray models were used to estimate cause-specific and subdistribution HRs, respectively, for loco-regional recurrence. Results: Of 390 cases, 266 (68.2%) were complete and 124 were incomplete anatomic segmentectomy. Demographics, pulmonary function, tumour size, stage and perioperative outcomes did not significantly differ between groups. Surgical margins were negative in all but 1 case. Complete anatomic segmentectomy was associated with improved lymph node dissection (5 vs 2 median nodes sampled; P < 0.001). Multivariable analysis revealed reduced incidence of loco-regional recurrence (cause-specific HR = 0.42; 95% confidence interval 0.22-0.80; subdistribution HR = 0.43; 95% confidence interval 0.23-0.81), and non-significant improvement in overall survival (HR = 0.66; 95% confidence interval: 0.43-1.00) after complete versus incomplete anatomic segmentectomy. Conclusions: This single-centre experience suggests complete anatomic segmentectomy provides superior loco-regional control and may improve survival relative to incomplete anatomic segmentectomy. We recommend surgeons perform complete anatomic segmentectomy and lymph node dissection whenever possible.
MeSH term(s)	Humans ; Lung Neoplasms ; Carcinoma, Non-Small-Cell Lung ; Pneumonectomy/methods ; Retrospective Studies ; Treatment Outcome ; Neoplasm Recurrence, Local/surgery ; Neoplasm Staging
Language	English
Publishing date	2024-02-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezae089
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