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Article ; Online: Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial.

2019 Volume 133, Issue 18, Page(s) 1964–1976

Abstract: ... with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP ... to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm ... in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP ...

Abstract	Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D). Fifty-six patients were enrolled, most with follicular lymphoma (43%) or diffuse large B-cell lymphoma (DLBCL; 32%). Dose-limiting toxicities were reported in 3/14 patients at the first venetoclax dose (200 mg/d), after which dosing was changed from daily to 10 days per cycle and escalated to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm. Cytopenias were predominant among grade 3/4 events and reported at a higher rate than expected, particularly in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP combinations); complete response (CR) rates were 79.2% and 78.1%, respectively. Most double-expressor (BCL2
MeSH term(s)	Aged ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Cyclophosphamide/therapeutic use ; Disease-Free Survival ; Doxorubicin/therapeutic use ; Female ; Humans ; Lymphoma, Non-Hodgkin/drug therapy ; Lymphoma, Non-Hodgkin/mortality ; Male ; Maximum Tolerated Dose ; Middle Aged ; Prednisone/therapeutic use ; Rituximab/therapeutic use ; Sulfonamides/therapeutic use ; Vincristine/therapeutic use
Chemical Substances	Antibodies, Monoclonal, Humanized ; Bridged Bicyclo Compounds, Heterocyclic ; R-CHOP protocol ; Sulfonamides ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; venetoclax (N54AIC43PW) ; obinutuzumab (O43472U9X8) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2019-03-08
Publishing country	United States
Document type	Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2018-11-880526
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Article ; Online: A Data-Rich Longitudinal Wellness Study for the Digital Age: Fixing a Broken Medical System Requires Data About Each Patient.

Glusman, Gustavo

IEEE pulse

2017 Volume 8, Issue 4, Page(s) 11–14

Abstract: We live in an age of plentiful information, collected continuously by pervasive gadgetry, distributed through digital and social networks, and mined deeply by ever-more-powerful analytics systems. And yet, one of the things we know the least about is our ...

Abstract	We live in an age of plentiful information, collected continuously by pervasive gadgetry, distributed through digital and social networks, and mined deeply by ever-more-powerful analytics systems. And yet, one of the things we know the least about is our bodies. When it comes to our own health, we are driving blindly. Modern medicine has clearly been remarkably successful, as evidenced by continually growing life expectancies. For example, the number of people 65 and older in the United States has seen a steady increase over the last century, rising from 3.1 million in 1900 to 41.4 million as of 2011-and is expected to grow to 80 million by 2040. Concurrently, the number (and fraction) of people suffering from chronic conditions is also growing, from 44.7% in 1995 to 47.7% in 2015-and expected to rise to over 49% by 2030 [1]. According to the U.S. Centers for Disease Control and Prevention, the vast majority of healthcare costs (86%) are spent on treating and managing chronic disease. Indeed, the medical field today focuses almost entirely on care after illness: modern medicine is largely reactive, waiting until the system fails before taking action. While the field of dentistry has fully embraced regular preventive evaluation and treatment with great success, most other medical fields have yet to do so. Yearly physical evaluations are recommended, but they rely on very limited data collection. As long as there are no symptoms, current standard medical practice largely foregoes testing (laboratory, imaging, etc.) as a screening method to detect disease before it manifests itself.
Language	English
Publishing date	2017-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2567191-1
ISSN	2154-2317 ; 2154-2287
ISSN (online)	2154-2317
ISSN	2154-2287
DOI	10.1109/MPUL.2016.2647038
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Article ; Online: Clinical applications of sequencing take center stage.

Glusman, Gustavo

Genome biology

2013 Volume 14, Issue 3, Page(s) 303

Abstract: A report on the Advances in Genome Biology and Technology (AGBT) meeting, Marco Island, Florida, USA, February 20-23, 2013. ...

Abstract	A report on the Advances in Genome Biology and Technology (AGBT) meeting, Marco Island, Florida, USA, February 20-23, 2013.
MeSH term(s)	Exome/genetics ; Humans ; Sequence Analysis, DNA/methods ; Translational Medical Research
Language	English
Publishing date	2013-03-28
Publishing country	England
Document type	Congress ; Research Support, Non-U.S. Gov't
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/gb-2013-14-3-303
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Article: Editorial: Personal Genomes: Accessing, Sharing, and Interpretation.

Corpas, Manuel / Beck, Stephan / Glusman, Gustavo / Shabani, Mahsa

Frontiers in genetics

2021 Volume 12, Page(s) 687584

Language	English
Publishing date	2021-06-04
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.687584
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Article ; Online: Opportunities and Challenges in Interpreting and Sharing Personal Genomes.

Rubin, Irit R / Glusman, Gustavo

Genes

2019 Volume 10, Issue 9

Abstract: The 2019 "Personal Genomes: Accessing, Sharing and Interpretation" conference (Hinxton, UK, 11-12 April 2019) brought together geneticists, bioinformaticians, clinicians and ethicists to promote openness and ethical sharing of personal genome data while ... ...

Abstract	The 2019 "Personal Genomes: Accessing, Sharing and Interpretation" conference (Hinxton, UK, 11-12 April 2019) brought together geneticists, bioinformaticians, clinicians and ethicists to promote openness and ethical sharing of personal genome data while protecting the privacy of individuals. The talks at the conference focused on two main topic areas: (1) Technologies and Applications, with emphasis on personal genomics in the context of healthcare. The issues discussed ranged from new technologies impacting and enabling the field, to the interpretation of personal genomes and their integration with other data types. There was particular emphasis and wide discussion on the use of polygenic risk scores to inform precision medicine. (2) Ethical, Legal, and Social Implications, with emphasis on genetic privacy: How to maintain it, how much privacy is possible, and how much privacy do people want? Talks covered the full range of genomic data visibility, from open access to tight control, and diverse aspects of balancing benefits and risks, data ownership, working with individuals and with populations, and promoting citizen science. Both topic areas were illustrated and informed by reports from a wide variety of ongoing projects, which highlighted the need to diversify global databases by increasing representation of understudied populations.
MeSH term(s)	Genetic Privacy/ethics ; Genetic Privacy/legislation & jurisprudence ; Genetic Privacy/standards ; Genome, Human ; Humans ; Information Dissemination
Language	English
Publishing date	2019-08-25
Publishing country	Switzerland
Document type	Congress
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes10090643
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Article: Leishmania donovani: characterization of a 38-kDa membrane protein that cross-reacts with the mammalian G-protein transducin.

Cassel, D / Shoubi, S / Glusman, G / Cukierman, E / Rotman, M / Zilberstein, D

Experimental parasitology

1991 Volume 72, Issue 4, Page(s) 411–417

Abstract: ... to the G-proteins known to mediate signal transduction in other organisms. [alpha 32P]GTP binding ... specificity. Experiments with antisera directed against mammalian G-proteins showed that the promastigotes ... containing the C-terminal sequence of transducin, the G-protein that mediates visual signal transduction ...

Abstract	We investigated the presence in Leishmania donovani promastigotes of proteins with homology to the G-proteins known to mediate signal transduction in other organisms. [alpha 32P]GTP binding experiments revealed the presence in the promastigote membrane of GTP-binding sites with high affinity and specificity. Experiments with antisera directed against mammalian G-proteins showed that the promastigotes possess a 38-kDa protein (p38) which strongly reacts with an antiserum directed against a decapeptide containing the C-terminal sequence of transducin, the G-protein that mediates visual signal transduction. The interaction of p38 with the antiserum is specifically blocked by the decapeptide antigen. p38 is enriched in plasma membranes and is absent in cytosol and in a mitochondria-enriched fraction. p38 was also detected in two other Leishmania species, L. mexicana and L. major. The migration of p38 upon sucrose gradient centrifugation of detergent extract of L. donovani membranes corresponded to Mr of approximately 70,000, indicating that p38 is part of an oligomeric structure. The findings suggest that p38 may be a component of a transmembrane signal transduction system in Leishmania.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antigens, Protozoan/analysis ; Antigens, Protozoan/immunology ; Binding Sites ; Cell Membrane/chemistry ; Cell Membrane/metabolism ; Cross Reactions ; Guanosine Triphosphate/metabolism ; Hydrogen-Ion Concentration ; Leishmania donovani/analysis ; Leishmania donovani/immunology ; Leishmania mexicana/analysis ; Leishmania tropica/analysis ; Membrane Proteins/analysis ; Membrane Proteins/immunology ; Molecular Sequence Data ; Molecular Weight ; Protozoan Proteins/analysis ; Protozoan Proteins/chemistry ; Protozoan Proteins/immunology ; Signal Transduction ; Transducin/analysis ; Transducin/immunology
Chemical Substances	Antigens, Protozoan ; Membrane Proteins ; Protozoan Proteins ; Guanosine Triphosphate (86-01-1) ; Transducin (EC 3.6.5.1)
Language	English
Publishing date	1991-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391089-1
ISSN	1090-2449 ; 0014-4894
ISSN (online)	1090-2449
ISSN	0014-4894
DOI	10.1016/0014-4894(91)90087-d
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Article: Genotype Fingerprints Enable Fast and Private Comparison of Genetic Testing Results for Research and Direct-to-Consumer Applications.

Robinson, Max / Glusman, Gustavo

Genes

2018 Volume 9, Issue 10

Abstract: Genetic testing has expanded out of the research laboratory into medical practice and the direct-to-consumer market. Rapid analysis of the resulting genotype data now has a significant impact. We present a method for summarizing personal genotypes as ' ... ...

Abstract	Genetic testing has expanded out of the research laboratory into medical practice and the direct-to-consumer market. Rapid analysis of the resulting genotype data now has a significant impact. We present a method for summarizing personal genotypes as 'genotype fingerprints' that meets these needs. Genotype fingerprints can be derived from any single nucleotide polymorphism-based assay, and remain comparable as chip designs evolve to higher marker densities. We demonstrate that these fingerprints support distinguishing types of relationships among closely related individuals and closely related individuals from individuals from the same background population, as well as high-throughput identification of identical genotypes, individuals in known background populations, and de novo separation of subpopulations within a large cohort through extremely rapid comparisons. Although fingerprints do not preserve anonymity, they provide a useful degree of privacy by summarizing a genotype while preventing reconstruction of individual marker states. Genotype fingerprints are therefore well-suited as a format for public aggregation of genetic information to support ancestry and relatedness determination without revealing personal health risk status.
Language	English
Publishing date	2018-10-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes9100481
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Article ; Online: Quality control of large genome datasets.

Robinson, Max / Joshi, Arpita / Vidyarthi, Ansh / Maccoun, Mary / Rangavajjhala, Sanjay / Glusman, Gustavo

HGG advances

2022 Volume 3, Issue 3, Page(s) 100123

Abstract: The 1000 Genomes Project (TGP) is a foundational resource that serves the biomedical community as a standard reference cohort for human genetic variation. There are now seven public versions of these genomes. The TGP Consortium produced the first by ... ...

Abstract	The 1000 Genomes Project (TGP) is a foundational resource that serves the biomedical community as a standard reference cohort for human genetic variation. There are now seven public versions of these genomes. The TGP Consortium produced the first by mapping its final data release against human reference sequence GRCh37, then "lifted over" these genomes to the improved reference sequence (GRCh38) when it was released, and remapped the original data to GRCh38 with two similar pipelines. As best-practice quality validation, the pipelines that generated these versions were benchmarked against the Genome In A Bottle Consortium's "platinum quality" genome (NA12878). The New York Genome Center recently released the results of independently resequencing the cohort at greater depth (30×), a phased version informed by the inclusion of related individuals, and independently remapped the original variant calls to GRCh38. We performed a cross-comparison evaluation of all seven versions using genome fingerprinting, which supports ultrafast genome comparison even across reference versions. We noted multiple issues, including discrepancies in cohort membership, disagreement on the overall level of variation, evidence of substandard pipeline performance on specific genomes and in specific regions of the genome, cryptic relationships between individuals, inconsistent phasing, and annotation distortions caused by the history of the reference genome itself. We therefore recommend global quality assessment by rapid genome comparisons, alongside benchmarking as part of best-practice quality assessment of large genome datasets. Our observations also help inform the decision of which version to use, to support analyses by individual researchers.
Language	English
Publishing date	2022-06-07
Publishing country	United States
Document type	Journal Article
ISSN	2666-2477
ISSN (online)	2666-2477
DOI	10.1016/j.xhgg.2022.100123
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Article ; Online: Cesarean versus vaginal delivery for breech presentation is an independent risk factor for long-term pediatric respiratory hospitalization of the offspring.

Davidesko, Sharon / Glusman Bendersky, Ahinoam / Levy, Amalia / Pariente, Gali / Landau, Daniella / Sheiner, Eyal

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics

2022 Volume 161, Issue 3, Page(s) 886–893

Abstract: Objectives: To compare the long-term respiratory morbidity of offspring born by cesarean delivery for breech presentation with that of those delivered vaginally.: Methods: A population-based cohort analysis including all singleton breech deliveries ... ...

Abstract	Objectives: To compare the long-term respiratory morbidity of offspring born by cesarean delivery for breech presentation with that of those delivered vaginally. Methods: A population-based cohort analysis including all singleton breech deliveries between the years 1991 and 2014, comparing long-term respiratory morbidity of offspring born in breech presentation, according to mode of delivery. Offspring with congenital malformations, perinatal deaths, and instrumental deliveries were excluded. Respiratory morbidity included hospitalizations (up to age 18 years), as recorded in hospital records. A Kaplan-Meier survival curve compared cumulative respiratory morbidity. A Weibull parametric survival model controlled for confounders and repeat deliveries. Results: A total of 7337 breech deliveries were included; 6376 (86.9%) cesarean deliveries and 961 (13.1%) vaginal breech deliveries. The Kaplan-Meier survival curve demonstrated higher cumulative incidence of respiratory morbidity in the cesarean delivery group compared with vaginal delivery (log rank test P = 0.006). Using a Weibull parametric survival model to control for confounders, cesarean delivery was found to be an independent risk factor for long-term respiratory morbidity of the offspring (adjusted hazard ratio 1.87, 95% confidence interval 1.32-2.65, P < 0.001). Conclusions: Cesarean versus vaginal delivery for breech presentation is an independent risk factor for long-term pediatric respiratory morbidity of the offspring.
MeSH term(s)	Pregnancy ; Female ; Humans ; Child ; Adolescent ; Breech Presentation/epidemiology ; Delivery, Obstetric/adverse effects ; Cesarean Section/adverse effects ; Risk Factors ; Hospitalization ; Retrospective Studies
Language	English
Publishing date	2022-11-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	80149-5
ISSN	1879-3479 ; 0020-7292
ISSN (online)	1879-3479
ISSN	0020-7292
DOI	10.1002/ijgo.14570
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Zs.A 355: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A Remotely Coached Multimodal Lifestyle Intervention for Alzheimer's Disease Ameliorates Functional and Cognitive Outcomes.

Roach, Jared C / Rapozo, Molly K / Hara, Junko / Glusman, Gwênlyn / Lovejoy, Jennifer / Shankle, William R / Hood, Leroy

Journal of Alzheimer's disease : JAD

2023 Volume 96, Issue 2, Page(s) 591–607

Abstract: Background: Comprehensive treatment of Alzheimer's disease and related dementias (ADRD) requires not only pharmacologic treatment but also management of existing medical conditions and lifestyle modifications including diet, cognitive training, and ... ...

Abstract	Background: Comprehensive treatment of Alzheimer's disease and related dementias (ADRD) requires not only pharmacologic treatment but also management of existing medical conditions and lifestyle modifications including diet, cognitive training, and exercise. Personalized, multimodal therapies are needed to best prevent and treat Alzheimer's disease (AD). Objective: The Coaching for Cognition in Alzheimer's (COCOA) trial was a prospective randomized controlled trial to test the hypothesis that a remotely coached multimodal lifestyle intervention would improve early-stage AD. Methods: Participants with early-stage AD were randomized into two arms. Arm 1 (N = 24) received standard of care. Arm 2 (N = 31) additionally received telephonic personalized coaching for multiple lifestyle interventions. The primary outcome was a test of the hypothesis that the Memory Performance Index (MPI) change over time would be better in the intervention arm than in the control arm. The Functional Assessment Staging Test was assessed for a secondary outcome. COCOA collected psychometric, clinical, lifestyle, genomic, proteomic, metabolomic, and microbiome data at multiple timepoints (dynamic dense data) across two years for each participant. Results: The intervention arm ameliorated 2.1 [1.0] MPI points (mean [SD], p = 0.016) compared to the control over the two-year intervention. No important adverse events or side effects were observed. Conclusion: Multimodal lifestyle interventions are effective for ameliorating cognitive decline and have a larger effect size than pharmacological interventions. Dietary changes and exercise are likely to be beneficial components of multimodal interventions in many individuals. Remote coaching is an effective intervention for early stage ADRD. Remote interventions were effective during the COVID pandemic.
MeSH term(s)	Humans ; Alzheimer Disease/therapy ; Prospective Studies ; Proteomics ; Life Style ; Cognitive Dysfunction/therapy ; Cognition
Language	English
Publishing date	2023-10-16
Publishing country	Netherlands
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-230403
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