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Article: Advances in Diagnosis and Risk Stratification of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Pillai, Raju K / Afkhami, Michelle

2021 Volume 181, Page(s) 1–16

Abstract: Advances in high-throughput DNA sequencing technology in the past decade have made a tremendous impact on basic science and clinical practice. Methods using the latest next generation sequencing technology can sequence an entire human genome within a few ...

Abstract	Advances in high-throughput DNA sequencing technology in the past decade have made a tremendous impact on basic science and clinical practice. Methods using the latest next generation sequencing technology can sequence an entire human genome within a few hours. Diagnosis and prognostication of hematologic neoplasms have moved from traditional histology and immunophenotyping to integration of cytogenetic and genomic alterations. Using illustrative cases, this chapter provides an overview of the utility of using genomic data for prognostication as well as treatment decision-making for patients with bone marrow neoplasms.
MeSH term(s)	Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/genetics ; Mutation ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/genetics ; Risk Assessment
Language	English
Publishing date	2021-10-09
Publishing country	United States
Document type	Journal Article
ISSN	0927-3042
ISSN	0927-3042
DOI	10.1007/978-3-030-78311-2_1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Streptococcus dysgalactiae Subspecies dysgalactiae Infection Presenting With Septic Shock.

Nathan, Balamurugan / Pillai, Vivekanandan / Ayyan, S Manu / Ss, Anuusha / Prakash Raju, K N J

Cureus

2021 Volume 13, Issue 1, Page(s) e12465

Abstract: Streptococcus ... ...

Abstract	Streptococcus dysgalactiae
Language	English
Publishing date	2021-01-03
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.12465
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Article: Genetics and Diagnostic Approach to Lymphoblastic Leukemia/Lymphoma.

Afkhami, Michelle / Ally, Feras / Pullarkat, Vinod / Pillai, Raju K

Cancer treatment and research

2021 Volume 181, Page(s) 17–43

Abstract: Our understanding of the genetics and biology of lymphoblastic leukemia/lymphoma (acute lymphoblastic leukemia, ALL) has advanced rapidly in the past decade with advances in sequencing and other molecular techniques. Besides recurrent chromosomal ... ...

Abstract	Our understanding of the genetics and biology of lymphoblastic leukemia/lymphoma (acute lymphoblastic leukemia, ALL) has advanced rapidly in the past decade with advances in sequencing and other molecular techniques. Besides recurrent chromosomal abnormalities detected by karyotyping or fluorescence in situ hybridization, these leukemias/lymphomas are characterized by a variety of mutations, gene rearrangements as well as copy number alterations. This is particularly true in the case of Philadelphia-like (Ph-like) ALL, a major subset which has the same gene expression signature as Philadelphia chromosome-positive ALL but lacks BCR-ABL1 translocation. Ph-like ALL is associated with a worse prognosis and hence its detection is critical. However, techniques to detect this entity are complex and are not widely available. This chapter discusses various subsets of ALL and describes our approach to the accurate classification and prognostication of these cases.
MeSH term(s)	Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
Language	English
Publishing date	2021-10-09
Publishing country	United States
Document type	Journal Article
ISSN	0927-3042
ISSN	0927-3042
DOI	10.1007/978-3-030-78311-2_2
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Article ; Online: Harnessing the Power of Induced Pluripotent Stem Cells and Gene Editing Technology: Therapeutic Implications in Hematological Malignancies.

Sidhu, Ishnoor / Barwe, Sonali P / Pillai, Raju K / Gopalakrishnapillai, Anilkumar

Cells

2021 Volume 10, Issue 10

Abstract: In vitro modeling of hematological malignancies not only provides insights into the influence of genetic aberrations on cellular and molecular mechanisms involved in disease progression but also aids development and evaluation of therapeutic agents. ... ...

Abstract	In vitro modeling of hematological malignancies not only provides insights into the influence of genetic aberrations on cellular and molecular mechanisms involved in disease progression but also aids development and evaluation of therapeutic agents. Owing to their self-renewal and differentiation capacity, induced pluripotent stem cells (iPSCs) have emerged as a potential source of short in supply disease-specific human cells of the hematopoietic lineage. Patient-derived iPSCs can recapitulate the disease severity and spectrum of prognosis dictated by the genetic variation among patients and can be used for drug screening and studying clonal evolution. However, this approach lacks the ability to model the early phases of the disease leading to cancer. The advent of genetic editing technology has promoted the generation of precise isogenic iPSC disease models to address questions regarding the underlying genetic mechanism of disease initiation and progression. In this review, we discuss the use of iPSC disease modeling in hematological diseases, where there is lack of patient sample availability and/or difficulty of engraftment to generate animal models. Furthermore, we describe the power of combining iPSC and precise gene editing to elucidate the underlying mechanism of initiation and progression of various hematological malignancies. Finally, we discuss the power of iPSC disease modeling in developing and testing novel therapies in a high throughput setting.
MeSH term(s)	Animals ; Clinical Trials as Topic ; Disease Models, Animal ; Gene Editing ; Hematologic Neoplasms/genetics ; Hematologic Neoplasms/therapy ; Hematopoiesis ; Humans ; Induced Pluripotent Stem Cells/metabolism
Language	English
Publishing date	2021-10-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10102698
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Article ; Online: Harnessing the Power of Induced Pluripotent Stem Cells and Gene Editing Technology

Ishnoor Sidhu / Sonali P. Barwe / Raju K. Pillai / Anilkumar Gopalakrishnapillai

Cells, Vol 10, Iss 2698, p

Therapeutic Implications in Hematological Malignancies

2021 Volume 2698

Abstract	In vitro modeling of hematological malignancies not only provides insights into the influence of genetic aberrations on cellular and molecular mechanisms involved in disease progression but also aids development and evaluation of therapeutic agents. Owing to their self-renewal and differentiation capacity, induced pluripotent stem cells (iPSCs) have emerged as a potential source of short in supply disease-specific human cells of the hematopoietic lineage. Patient-derived iPSCs can recapitulate the disease severity and spectrum of prognosis dictated by the genetic variation among patients and can be used for drug screening and studying clonal evolution. However, this approach lacks the ability to model the early phases of the disease leading to cancer. The advent of genetic editing technology has promoted the generation of precise isogenic iPSC disease models to address questions regarding the underlying genetic mechanism of disease initiation and progression. In this review, we discuss the use of iPSC disease modeling in hematological diseases, where there is lack of patient sample availability and/or difficulty of engraftment to generate animal models. Furthermore, we describe the power of combining iPSC and precise gene editing to elucidate the underlying mechanism of initiation and progression of various hematological malignancies. Finally, we discuss the power of iPSC disease modeling in developing and testing novel therapies in a high throughput setting.
Keywords	iPSC ; gene editing ; hematologic ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Myeloid lineage switch following CD7-targeted chimeric antigen receptor T-cell therapy in relapsed/refractory T-cell acute lymphoblastic leukemia.

Aldoss, Ibrahim / Tizro, Parastou / Bedi, Davsheen / Mangan, James K / Clark, Mary C / Spencer, David / Song, Joo Y / Cherian, Sindhu / Pillai, Raju / Kim, Young / Mahajan, Nitin / Gendzekhadze, Ketevan / James, Mike / Jacobs, Kenneth / Davidson-Moncada, Jan / Forman, Stephen J / Wang, Huan-You / Afkhami, Michelle

Haematologica

2023 Volume 108, Issue 12, Page(s) 3511–3516

MeSH term(s)	Humans ; Receptors, Chimeric Antigen/genetics ; Cell Lineage ; Immunotherapy, Adoptive ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy ; T-Lymphocytes ; Cell- and Tissue-Based Therapy ; Antigens, CD19
Chemical Substances	Receptors, Chimeric Antigen ; Antigens, CD19
Language	English
Publishing date	2023-12-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.283566
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Article ; Online: Indian Society of Pediatric Neurosurgery Consensus Guidelines on Preventing and Managing Shunt Infection: Version 2020-21.

Udayakumaran, Suhas / Pillai, Shibu / Dwarakanath, Srinivas / Bhattacharjee, Suchanda / Mehrotra, Naveen / Raju, Subodh / Gupta, Deepak / Panigrahi, Manas / Venkataramana, Neelam K / Rajshekhar, Vedantam / Sankhla, Suresh

Neurology India

2022 Volume 69, Issue Supplement, Page(s) S526–S555

Abstract: Background: Shunt infection is the most significant morbidity associated with shunt surgery. Based on the existing literature for the prevention and management of shunt infection, region and resource-specific recommendations are needed.: Methods: In ... ...

Abstract	Background: Shunt infection is the most significant morbidity associated with shunt surgery. Based on the existing literature for the prevention and management of shunt infection, region and resource-specific recommendations are needed. Methods: In February 2020, a Guidelines Development Group (GDG) was created by the Indian Society of Paediatric Neurosurgery (IndSPN) to formulate guidelines on shunt infections, which would be relevant to our country and LMIC in general. An initial email survey identified existing practices among the membership of the IndSPN, and eight broad issues pertaining to shunt infection were identified. Next, members of the GDG performed a systematic review of the literature on the prevention and management of shunt infection. Then, through a series of virtual meetings of the GDG over 1 year, evidence from the literature was presented to all the members and consensus was built on different aspects of shunt infection. Finally, the guidelines document was drafted and circulated among the GDG for final approval. Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to grade the evidence and strength of recommendation. Results: The guidelines are divided into eight sections. Level I and Level II evidence was available for only five recommendations and led to a moderate level of recommendations. Most of the available evidence was at Level III and below, and hence the level of recommendation was low or very low. A consensus method was used to provide recommendations for several issues. Conclusions: Although most of the recommendations for the prevention and management of shunt infections are based on a low level of evidence, we believe that this document will provide a useful reference to neurosurgeons not only in India but also in other low and middle income countries. These guidelines need to be updated as and when new evidence emerges.
MeSH term(s)	Child ; Consensus ; Humans ; India ; Neurosurgery ; Neurosurgical Procedures/adverse effects ; Societies
Language	English
Publishing date	2022-01-28
Publishing country	India
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	415522-1
ISSN	1998-4022 ; 0028-3886
ISSN (online)	1998-4022
ISSN	0028-3886
DOI	10.4103/0028-3886.332268
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Article ; Online: Determination of age-dependent bone marrow normocellularity.

Wong, Jerry / Jackson, Ryan / Chen, Lu / Song, Joo / Pillai, Raju / Afkhami, Michelle / Danilova, Olga / Aoun, Patricia / Gaal, Karl K / Kim, Young

American journal of clinical pathology

2023 Volume 161, Issue 2, Page(s) 170–176

Abstract: Objectives: Determination of bone marrow cellularity is a key part of bone marrow examination because it provides a small window into a patient's current state of hematopoietic well-being. Traditionally, bone marrow cellularity is estimated ... ...

Abstract	Objectives: Determination of bone marrow cellularity is a key part of bone marrow examination because it provides a small window into a patient's current state of hematopoietic well-being. Traditionally, bone marrow cellularity is estimated semiquantitatively through microscopic examination of core biopsy specimens harvested from the iliac crest of the pelvic bone. Bone marrow cellularity is then designated as hypercellular, normocellular, or hypocellular based on the patient's age. This assessment can have significant clinical impact, but the variation in the age-adjusted normocellularity range is not sufficiently characterized because of a lack of study data, especially in older patients (those older than 70 years of age). This study further established the normal range of bone marrow cellularity, particularly in older adults. Methods: In this study, 570 benign staging and healthy donor bone marrows from patients 1 year to 93 years of age were analyzed for cellularity. Results: Linear regression modeling demonstrates that cellularity in adults declines approximately 3% per decade, including after the seventh decade of life. The 90% reference interval for normocellularity in United States is 30% to 75% for those aged 18 to 90 years. Conclusions: The findings revealed a more stable and slower rate of decline in cellularity with age in adults than the widely used linear model of "100% minus the patient age in decades." Normocellularity is better modeled based on age group. In those younger than 20 years of age, normocellularity ranges from 45% to 85% (mean [SD], 65% [20%]), as defined by Friebert et al in 1998. Based on our study finding of a little less than 3% decline per decade of age, the following is our recommendation for normocellularity range: For individuals 20 to 40 years of age, it ranges from 40% to 70% (mean [SD], 55% [15%]); for individuals 40 to 60 years of age, it ranges from 35% to 65% (mean [SD], 50% [15%]); and for individuals older than 60 years of age, it ranges from 30% to 60% (mean [SD], 45% [15%]). Interestingly, those older than 70 years of age do not show a significant decrease from those aged 60 to 69 years.
MeSH term(s)	Humans ; Aged ; Young Adult ; Adult ; Infant ; Bone Marrow/pathology ; Bone Marrow Examination ; Bone Marrow Cells/pathology ; Biopsy, Large-Core Needle ; Hyperplasia/pathology
Language	English
Publishing date	2023-10-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2944-0
ISSN	1943-7722 ; 0002-9173
ISSN (online)	1943-7722
ISSN	0002-9173
DOI	10.1093/ajcp/aqad129
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Article ; Online: Genetic characterization and drug sensitivity study of newly derived HGBL double/triple-hit lymphoma cell lines.

Zhang, Jibin / Wang, Tingting / Shetty, Kunal / Alkan, Serhan / Xu, Senlin / Gong, Qiang / Liu, Xuxiang / Li, Yuping / Hu, Zunsong / Huang, Wendong / Wendel, Hans-Guido / Herrera, Alex F / Pillai, Raju K / Song, Joo Y / Chan, Wing C

Blood advances

2022 Volume 6, Issue 17, Page(s) 5067–5071

MeSH term(s)	Cell Line ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology
Language	English
Publishing date	2022-06-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021006709
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Article: HPV genotyping by L1 amplicon sequencing of archived invasive cervical cancer samples: a pilot study.

Warden, Charles D / Cholli, Preetam / Qin, Hanjun / Guo, Chao / Wang, Yafan / Kancharla, Chetan / Russell, Angelique M / Salvatierra, Sylvana / Mutsvunguma, Lorraine Z / Higa, Kerin K / Wu, Xiwei / Wilczynski, Sharon / Pillai, Raju / Ogembo, Javier Gordon

Infectious agents and cancer

2022 Volume 17, Issue 1, Page(s) 44

Abstract: Background: Human papillomavirus (HPV) is the primary cause of invasive cervical cancer (ICC). The prevalence of various HPV genotypes, ranging from oncogenically low- to high-risk, may be influenced by geographic and demographic factors, which could ... ...

Abstract	Background: Human papillomavirus (HPV) is the primary cause of invasive cervical cancer (ICC). The prevalence of various HPV genotypes, ranging from oncogenically low- to high-risk, may be influenced by geographic and demographic factors, which could have critical implications for the screening and prevention of HPV infection and ICC incidence. However, many technical factors may influence the identification of high-risk genotypes associated with ICC in different populations. Methods: We used high-throughput sequencing of a single amplicon within the HPV L1 gene to assess the influence of patient age, race/ethnicity, histological subtype, sample type, collection date, experimental factors, and computational parameters on the prevalence of HPV genotypes detected in archived DNA (n = 34), frozen tissue (n = 44), and formalin-fixed paraffin-embedded (FFPE) tissue (n = 57) samples collected in the Los Angeles metropolitan area. Results: We found that the percentage of off-target human reads and the concentration of DNA amplified from each sample varied by HPV genotype and by archive type. After accounting for the percentage of human reads and excluding samples with especially low levels of amplified DNA, the HPV prevalence was 95% across all ICC samples: HPV16 was the most common genotype (in 56% of all ICC samples), followed by HPV18 (in 21%). Depending upon the genotyping parameters, the prevalence of HPV58 varied up to twofold in our cohort. In archived DNA and frozen tissue samples, we detected previously established differences in HPV16 and HPV18 frequencies based on histological subtype, but we could not reproduce those findings using our FFPE samples. Conclusions: In this pilot study, we demonstrate that sample collection, preparation, and analysis methods can influence the detection of certain HPV genotypes and must be carefully considered when drawing any biological conclusions based on HPV genotyping data from ICC samples.
Language	English
Publishing date	2022-08-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2251117-9
ISSN	1750-9378
ISSN	1750-9378
DOI	10.1186/s13027-022-00456-w
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