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  1. Article ; Online: Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E.

    Chen, Eric X / Kavan, Petr / Tehfe, Mustapha / Kortmansky, Jeremy S / Sawyer, Michael B / Chiorean, E Gabriela / Lieu, Christopher H / Polite, Blase / Wong, Lucas / Fakih, Marwan / Spencer, Kristen / Chaves, Jorge / Li, Chenxiang / Leconte, Pierre / Adelberg, David / Kim, Richard

    Clinical colorectal cancer

    2024  

    Abstract: Background: Cohorts A, C, and E of the phase Ib KEYNOTE-651 study evaluated pembrolizumab ... oxaliplatin (cohort C; previously untreated) or 5-fluorouracil, leucovorin, irinotecan (cohort E; previously ... had DLTs with binimetinib 30 mg; dose was not escalated to 45 mg. In cohort E, 1/5 patients (20%) had ...

    Abstract Background: Cohorts A, C, and E of the phase Ib KEYNOTE-651 study evaluated pembrolizumab + binimetinib ± chemotherapy in microsatellite stable/mismatch repair-proficient metastatic colorectal cancer.
    Patients and methods: Patients received pembrolizumab 200 mg every 3 weeks plus binimetinib 30 mg twice daily alone (cohort A; previously treated with any chemotherapy) or with 5-fluorouracil, leucovorin, oxaliplatin (cohort C; previously untreated) or 5-fluorouracil, leucovorin, irinotecan (cohort E; previously treated with 1 line of therapy including fluoropyrimidine + oxaliplatin-based regimen) every 2 weeks. Binimetinib dose-escalation to 45 mg twice daily was planned in all cohorts using a modified toxicity probability interval design (target dose-limiting toxicity [DLT], 30%). The primary endpoint was safety; investigator-assessed objective response rate was secondary.
    Results: In cohort A, 1/6 patients (17%) had DLTs with binimetinib 30 mg; none occurred in 14 patients with 45 mg. In cohort C, 3/9 patients (33%) had DLTs with binimetinib 30 mg; dose was not escalated to 45 mg. In cohort E, 1/5 patients (20%) had DLTs with binimetinib 30 mg; 5/10 patients (50%) had DLTs with 45 mg. Enrollment was stopped in cohort E binimetinib 45 mg and deescalated to 30 mg; 2/4 additional patients (50%) had DLTs with binimetinib 30 mg (total 3/9 [33%] had DLTs with binimetinib 30 mg). Objective response rate was 0% in cohort A, 9% in cohort C, and 15% in cohort E.
    Conclusion: Per DLT criteria, binimetinib + pembrolizumab (cohort A) was tolerable, binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, oxaliplatin (cohort C) did not qualify for binimetinib dose escalation to 45 mg, and binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, irinotecan (cohort E) required binimetinib dose reduction from 45 to 30 mg. No new safety findings were observed across cohorts. There was no apparent additive efficacy when binimetinib + pembrolizumab was added to chemotherapy. Data did not support continued enrollment in cohorts C and E.
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2112638-0
    ISSN 1938-0674 ; 1533-0028
    ISSN (online) 1938-0674
    ISSN 1533-0028
    DOI 10.1016/j.clcc.2024.03.002
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  2. Article: Bioreactors and “smart vessels” for large-scale propagation

    Adelberg, J

    Acta horticulturae. 2017 Nov. 25, , no. 1187

    2017  

    Abstract: ... Micropropagation in liquid medium often has better growth than semi-solid “gels” (e.g. agar) due to the increased ...

    Abstract Producing plant material that is true-to-type and free of pests is a difficult task in clonally propagated crops. The biotechnology tools based on “agar-gels” work well in the laboratory, but does not serve the scale or allow physiological transitioning of plants to outdoor field conditions. Micropropagation in liquid medium often has better growth than semi-solid “gels” (e.g. agar) due to the increased availability of water and solutes when shoots are properly aerated. Bioreactors are mechanical vessels that facilitate gas exchange and media supplementation. Ergonomic complexity and cost of mechanical systems are balanced against anticipated improvements in growth. Mechanical rockers and pumped intermittent immersion systems increase the interfacial transfer surface that benefit growth. Larger vessels maximize growth area serviced by the mechanized devices. A wide variety of horticultural crops and mechanical devices illustrate these points. Simple systems, such as stationary thin films and support matrices often yield similar superior quality growth without the complexities and costs of mechanized agitated liquids. “Smart vessels” enable varied levels of air exchange, transitions from heterotrophic to photo-autotrophic environments, and materials handling in a less laborious, or more mechanized format. Manufactured matrices replace agar, have large macro-pores for oxygenated root zones, and allow two-dimensional arrays to be mechanically handled. Our laboratory has designed, and prototyped bioreactors and vessel systems to bridge the gap between biotechnology and field production.
    Keywords agar ; air ; bioreactors ; culture media ; gas exchange ; horticultural crops ; liquids ; materials handling ; mechanization ; micropropagation ; shoots ; solutes
    Language English
    Dates of publication 2017-1125
    Size p. 123-138.
    Publishing place International Society for Horticultural Science.
    Document type Article
    Note Paper presented at the IX International Symposium on In Vitro Culture and Horticultural Breeding held March 13 – 17 2016, Giza, Egypt
    ISSN 0567-7572
    DOI 10.17660/ActaHortic.2017.1187.15
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  3. Article: Micropropagation in liquid culture using partial immersion systems

    Adelberg, J. W

    Acta horticulturae. 2016 Mar. 22, , no. 1113

    2016  

    Abstract: Plant tissue culture in liquid medium often has better growth than in semi-solid “gels” (e.g ...

    Abstract Plant tissue culture in liquid medium often has better growth than in semi-solid “gels” (e.g., agar) due to the increased availability of water and solutes. Aerating shoots is necessary to prevent hyperhydricity and anoxia. Choosing a mechanical system for aeration involves increased cost, mechanical complexity and ergonomic problems, balanced against the anticipated improvements in growth responses. Larger vessels are used with these machines to increase the growth area serviced by the more complex mechanized devices. A wide variety of horticultural crops and mechanical devices will be shown to illustrate these points. Simple systems, such as stationary thin films and support matrices often yield quality growth without the complexities and costs of mechanized agitated liquids if interfacial transport properties of media and tissue are correctly incorporated. Mechanical rockers and pumped intermittent immersion systems increase the interfacial transfer surface that may further benefit growth. Two simple systems are demonstrated in this paper. A thin film system for Miscanthus × giganteus was shown to confer the advantages of both TIS and Rocker bioreactors. A novel vessel systems based on Oasis®foam and a flexible film vessel was shown to combine stage III and acclimatization of Hydrangea, resulting in faster growing greenhouse plants. As better materials become available, simpler systems will also be more readily available.
    Keywords acclimation ; aeration ; agar ; bioreactors ; gels ; greenhouses ; horticultural crops ; Hydrangea ; hyperhydricity ; hypoxia ; mechanization ; micropropagation ; Miscanthus giganteus ; plant tissues ; shoots ; solutes ; tissue culture
    Language English
    Dates of publication 2016-0322
    Size p. 35-46.
    Publishing place International Society for Horticultural Science.
    Document type Article
    Note Paper presented at the XXIX International Horticultural Congress on Horticulture: Sustaining Lives, Livelihoods and Landscapes (IHC 2014): International Symposium on Micropropagation and in Vitro Techniques held August 17-22, 2014, Brisbane, Australia
    ISSN 0567-7572
    DOI 10.17660/ActaHortic.2016.1113.5
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  4. Article: In vitro co-culture system for Prunus spp. and Armillaria mellea in phenolic foam rooting matric

    Adelberg, Jeffrey / Naylor-Adelberg, Jacqueline / Miller, Sarah / Gasic, Ksenija / Schnabel, Guido / Bryson, Patricia / Saski, Christopher / Parris, Stephen / Reighard, Gregory

    In vitro cellular & developmental biology. 2021 June, v. 57, no. 3

    2021  

    Abstract: ... resistant and susceptible rootstocks (i.e., common garden experiment) and minimizes variation in inoculum ...

    Abstract Armillaria and Desarmillaria spp. are causal agents of a devastating root-borne disease of peach. Breeding resistant rootstock requires a reliable screening tool. An in vitro co-culture screen designed for almond was modified by replacing agar-gelled medium with a more aerated phenolic foam and combining resistant and susceptible rootstocks (i.e., common garden experiment) and minimizes variation in inoculum pressure or rooting substrate among replicate vessels. Eight Prunus rootstocks tested (peach, plum, peach × plum, and choke cherry) were rooted and had no decline in health. Susceptible peach rootstock, ‘GF 305’, was cultured for 15 wk in phenolic foam in the same vessel with a resistant peach × plum hybrid, ‘MP-29’, inoculated with Armillaria mellea at week 5, that led to more severe shoot symptoms in the former after an additional 8 wk. This method accommodated peach genotypes that were difficult to root in agar medium. The difference during a uniform challenge with the A. mellea fungus recapitulates resistant/susceptible reactions. The phenolic foam-based co-culture method will work on many Prunus spp. of potential use in rootstock breeding.
    Keywords Armillaria mellea ; agar ; almonds ; cherries ; coculture ; decline ; foams ; fungi ; inoculum ; peaches ; plums ; rootstocks
    Language English
    Dates of publication 2021-06
    Size p. 387-397.
    Publishing place Springer US
    Document type Article
    Note NAL-AP-2-clean
    ISSN 1054-5476
    DOI 10.1007/s11627-020-10136-2
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  5. Article ; Online: Primary Care Physician Networks In Medicare Advantage.

    Feyman, Yevgeniy / Figueroa, José F / Polsky, Daniel E / Adelberg, Michael / Frakt, Austin

    Health affairs (Project Hope)

    2019  Volume 38, Issue 4, Page(s) 537–544

    Abstract: Medicare Advantage (MA) plans often establish restrictive networks of covered providers. Some policy makers have raised concerns that networks may have become excessively restrictive over time, potentially interfering with patients' access to providers. ... ...

    Abstract Medicare Advantage (MA) plans often establish restrictive networks of covered providers. Some policy makers have raised concerns that networks may have become excessively restrictive over time, potentially interfering with patients' access to providers. Because of data limitations, little is known about the breadth of MA networks. Taking a novel approach, we used Medicare Part D claims data for 2011-15 to examine how primary care physician networks have changed over time and what demographic and plan characteristics are associated with varying levels of network breadth. Our findings indicate that the share of MA plans with broad networks increased from 80.1 percent in 2011 to 82.5 percent in 2015. Enrollment in broad-network plans grew from 54.1 percent to 64.9 percent over the same period. In an adjusted analysis, we detected no significant time trend. In addition, narrow networks were associated with urbanicity, higher income, higher physician density, and more competition among plans. Health maintenance organizations had narrower networks than did point-of-service plans, whose networks were narrower than those of preferred provider organizations.
    MeSH term(s) Aged ; Aged, 80 and over ; Fee-for-Service Plans/economics ; Female ; Health Expenditures ; Humans ; Insurance Claim Review ; Male ; Medicare Part C/economics ; Medicare Part C/statistics & numerical data ; Outcome Assessment, Health Care ; Physicians, Primary Care/economics ; Physicians, Primary Care/statistics & numerical data ; Preferred Provider Organizations/economics ; Preferred Provider Organizations/statistics & numerical data ; Primary Health Care/economics ; Retrospective Studies ; Rural Population ; United States ; Urban Population
    Language English
    Publishing date 2019-04-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632712-6
    ISSN 1544-5208 ; 0278-2715
    ISSN (online) 1544-5208
    ISSN 0278-2715
    DOI 10.1377/hlthaff.2018.05501
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    Zs.A 2118: Show issues Location:
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  6. Article: Sucrose, water and nutrient use during stage II multiplication of two turmeric clones (Curcuma longa L.) in liquid medium

    Adelberg, Jeffrey

    Scientia horticulturae. 2010 Mar. 15, v. 124, no. 2

    2010  

    Abstract: ... In batch culture, the concentration of a nutrient that is rapidly used (e.g. sucrose) does not remain at an optimal ...

    Abstract Two clones of turmeric (Cucruma longa L.) were assessed nine times during a 28-day culture period in double phosphate MS liquid medium containing 2%, 4% and 6% sucrose. The phase of rapid shoot bud multiplication lasted for 21 days or less, in both clones in all media. The maximum multiplication rate was 3.4× at 20 and 19 days, with 3.9% or 4.7% initial sucrose concentration being optimal for the clones 9-3 and 35-1, respectively. Dry mass increased over the entire culture period and was greatest with 4.8% or at least 6% initial sucrose concentration for the two clones, 9-3 and 35-1, respectively. Maximum tissue water mass required 2.8% and 3.9% initial sucrose, respectively, in the two clones. Tissue relative water content (tissue water mass/fresh mass) was better correlated with sucrose concentration in medium, than the osmolality of medium, for both clones at all sucrose concentrations. Relative water content increased over time (water was incorporated more rapidly than dry mass in growing tissue) and sucrose concentration in media decreased over time (sucrose was used at a relatively more rapid rate than water). The concentrations of 10 nutrients (P, K, S, Zn, Mg, Fe, B, Ca, Mn and Cu) and Na assayed in time course all decreased rapidly over time. The rates of nutrient use were better related to growth of plant mass than shoot bud multiplication. P and Cu were completely depleted from medium before the end of the culture period. P concentration in tissues was in the lower ranges of that considered optimal, and Cu was in excess concentrations, based on comparison to high-yielding field-grown plants. Sugar, water, and nutrient use were more closely related to plant mass than shoot multiplication. The stationary phase of bud multiplication was coincident with continued growth of tissue dry and water mass. Among inorganic nutrients, lowered concentrations of P were most likely related to the stationary phase of bud multiplication, but still permissive of dry and water mass increases. Lowered availability of sugar, other inorganic nutrients, or less available water, did not precede day 21 and the end of active shoot bud multiplication. In batch culture, the concentration of a nutrient that is rapidly used (e.g. sucrose) does not remain at an optimal range for a prolonged period of time.
    Keywords Curcuma longa ; turmeric ; specialty crops ; clones ; micropropagation ; culture media ; sucrose ; water uptake ; plant nutrition ; in vitro regeneration ; water content ; dry matter accumulation ; osmolality ; nutrient availability ; temporal variation ; shoots ; buds ; nutrient use efficiency ; adventitious shoots
    Language English
    Dates of publication 2010-0315
    Size p. 262-267.
    Publishing place [Amsterdam; New York, NY]: Elsevier Science
    Document type Article
    ZDB-ID 185557-8
    ISSN 0304-4238
    ISSN 0304-4238
    DOI 10.1016/j.scienta.2009.12.027
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    Z 2810: Show issues

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  7. Article: Selection of bacterial mutants which excrete antagonists of antimetabolites.

    ADELBERG, E A

    Journal of bacteriology

    2003  Volume 76, Issue 3, Page(s) 326

    MeSH term(s) Antimetabolites ; Escherichia coli
    Chemical Substances Antimetabolites
    Language English
    Publishing date 2003-08-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/jb.76.3.326-326.1958
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  8. Article: The use of metabolically blocked organisms for the analysis of biosynthetic pathways.

    ADELBERG, E A

    Bacteriological reviews

    2003  Volume 17, Issue 4, Page(s) 253–267

    MeSH term(s) Biochemical Phenomena ; Biosynthetic Pathways ; Metabolism ; Microbiology
    Language English
    Publishing date 2003-08-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207943-4
    ISSN 0005-3678
    ISSN 0005-3678
    DOI 10.1128/br.17.4.253-267.1953
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  9. Article: Studies on the isoleucine precursor alpha, beta-dihydroxy-beta-ethylbutyric acid.

    ADELBERG, E A

    Journal of bacteriology

    2003  Volume 61, Issue 3, Page(s) 365–373

    MeSH term(s) Butyrates ; Butyric Acid ; Isoleucine ; Leucine
    Chemical Substances Butyrates ; Isoleucine (04Y7590D77) ; Butyric Acid (107-92-6) ; Leucine (GMW67QNF9C)
    Language English
    Publishing date 2003-11-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/jb.61.3.365-373.1951
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  10. Article: The biosynthesis of isoleucine and valine. III. Tracer experiments with L-threonine.

    ADELBERG, E A

    The Journal of biological chemistry

    2003  Volume 216, Issue 1, Page(s) 431–437

    MeSH term(s) Isoleucine ; Leucine/analogs & derivatives ; Neurospora ; Threonine/metabolism ; Valine/metabolism
    Chemical Substances Isoleucine (04Y7590D77) ; Threonine (2ZD004190S) ; Leucine (GMW67QNF9C) ; Valine (HG18B9YRS7)
    Language English
    Publishing date 2003-05-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
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