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  1. Article ; Online: Poor Encoding and Weak Early Consolidation Underlie Memory Acquisition Deficits in Multiple Sclerosis: Retroactive Interference, Processing Speed, or Working Memory?

    Sandry, Joshua / Zuppichini, Mark / Rothberg, Jessica / Valdespino-Hayden, Zerbrina / DeLuca, John

    Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists

    2017  Volume 34, Issue 2, Page(s) 162–182

    Abstract: Objective: Learning and memory impairments are common in multiple sclerosis (MS) and may be related to difficulty acquiring (encoding or consolidating) new information. We evaluate the role of retroactive interference and investigate whether minimizing ... ...

    Abstract Objective: Learning and memory impairments are common in multiple sclerosis (MS) and may be related to difficulty acquiring (encoding or consolidating) new information. We evaluate the role of retroactive interference and investigate whether minimizing interference immediately following encoding (early during consolidation) will improve MS participants' ability to remember new verbal information. Additionally, we investigate processing speed differences between memory-impaired and unimpaired participants and present an exploratory analysis of how the dual-components of working memory (capacity vs. processing) relate to memory impairment.
    Method: MS memory-unimpaired (N = 12) and MS memory-impaired participants (N = 12) were compared to healthy controls (N = 15). Interference onset following encoding (early, mid, late, no interference) was manipulated over the retention interval of a verbal learning and memory task. Response times (RT) were recorded during interference trials.
    Results: MS memory-impaired participants encoded less information and lost proportionally more information over the retention interval (weak consolidation). Lengthening the onset of interference did not benefit memory performance in this sample. Memory performance was unrelated to RT but was related to performance on the Symbol Digit Modalities Test. Primary capacity of working memory did not differ across groups; however, secondary memory processing was reduced for MS memory-impaired participants.
    Conclusion: Minimizing interference following encoding did not improve memory in this sample. Both initial encoding and early consolidation were reduced for memory-impaired MS participants. Evidence for a relationship between processing speed and memory was mixed and depended on the processing speed assessment used. Memory impairment in MS may be partially due to inefficient processing within working memory.
    MeSH term(s) Adult ; Case-Control Studies ; Female ; Humans ; Male ; Memory Consolidation/physiology ; Memory Disorders/complications ; Memory Disorders/psychology ; Memory, Short-Term/physiology ; Middle Aged ; Multiple Sclerosis/complications ; Multiple Sclerosis/psychology ; Neuropsychological Tests ; Reaction Time/physiology
    Language English
    Publishing date 2017-12-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632972-x
    ISSN 1873-5843 ; 0887-6177
    ISSN (online) 1873-5843
    ISSN 0887-6177
    DOI 10.1093/arclin/acy029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Bioinformatics. Introduction.

    Rothberg, Jonathan / Merriman, Barry / Higgs, Gadareth

    The Yale journal of biology and medicine

    2012  Volume 85, Issue 3, Page(s) 305–308

    MeSH term(s) Computational Biology/education ; Computational Biology/methods ; Databases, Genetic ; Genome, Human ; Humans ; Neoplasms/genetics ; Oligonucleotide Array Sequence Analysis/instrumentation ; Oligonucleotide Array Sequence Analysis/methods ; Sequence Analysis, DNA ; Statistics as Topic/methods
    Language English
    Publishing date 2012-11-23
    Publishing country United States
    Document type Introductory Journal Article
    ZDB-ID 200515-3
    ISSN 1551-4056 ; 0044-0086
    ISSN (online) 1551-4056
    ISSN 0044-0086
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Suicide statistics.

    Rothberg, J M

    Suicide & life-threatening behavior

    1999  Volume 29, Issue 3, Page(s) 286

    MeSH term(s) Humans ; Police/statistics & numerical data ; Queensland/epidemiology ; Suicide/statistics & numerical data
    Language English
    Publishing date 1999
    Publishing country England
    Document type Comment ; Letter
    ZDB-ID 750058-0
    ISSN 1943-278X ; 0363-0234 ; 0047-4592
    ISSN (online) 1943-278X
    ISSN 0363-0234 ; 0047-4592
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The Army psychological autopsy: then and now.

    Rothberg, J M

    Military medicine

    1998  Volume 163, Issue 6, Page(s) 427–433

    Abstract: The conduct and reporting of an Army psychological autopsy is a complex and relatively infrequent event. The details of these reports may not be completely clear to the behavioral sciences personnel tasked with collecting the data. This paper reviews the ...

    Abstract The conduct and reporting of an Army psychological autopsy is a complex and relatively infrequent event. The details of these reports may not be completely clear to the behavioral sciences personnel tasked with collecting the data. This paper reviews the current status of the Army psychological autopsy and contrasts it with the development of civilian psychological autopsies. The current thinking of the Department of Defense Health Affairs working group on psychological autopsies is presented. The epidemiological content of the Army psychological autopsy as a scientific resource is presented in the form of an analysis of the psychological autopsies for the 1995 Army suicide data. Suggestions for updating this unique command tool are included.
    MeSH term(s) Adolescent ; Adult ; Female ; Humans ; Male ; Military Personnel ; Military Psychiatry ; Suicide/psychology ; United States
    Language English
    Publishing date 1998-06
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 391061-1
    ISSN 1930-613X ; 0026-4075
    ISSN (online) 1930-613X
    ISSN 0026-4075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: LAM-003, a new drug for treatment of tyrosine kinase inhibitor-resistant FLT3-ITD-positive AML.

    Beeharry, Neil / Landrette, Sean / Gayle, Sophia / Hernandez, Marylens / Grotzke, Jeff E / Young, Peter R / Beckett, Paul / Zhang, Xuan / Carter, Bing Z / Andreeff, Michael / Halene, Stephanie / Xu, Tian / Rothberg, Jonathan / Lichenstein, Henri

    Blood advances

    2019  Volume 3, Issue 22, Page(s) 3661–3673

    Abstract: Acute myeloid leukemias (AML) harboring a constitutively active internal tandem duplication (ITD) mutation in the FMS-like kinase tyrosine kinase (FLT3) receptor are associated with poor patient prognosis. Despite initial clinical responses to FLT3 ... ...

    Abstract Acute myeloid leukemias (AML) harboring a constitutively active internal tandem duplication (ITD) mutation in the FMS-like kinase tyrosine kinase (FLT3) receptor are associated with poor patient prognosis. Despite initial clinical responses to FLT3 kinase inhibitors, patients eventually relapse. Mechanisms of resistance include the acquisition of secondary FLT3 mutations and protective stromal signaling within the bone marrow niche. Here we show that LAM-003, a prodrug of the heat shock protein 90 inhibitor LAM-003A, has cytotoxic activity against AML cell lines and primary samples harboring FLT3-ITD. LAM-003 regressed tumors in an MV-4-11 xenograft mouse model and extended survival in a MOLM-13 systemic model. LAM-003 displayed synergistic activity with chemotherapeutic drugs and FLT3 inhibitors, with the most robust synergy being obtained with venetoclax, a BCL-2 inhibitor. This finding was verified in a MOLM-13 systemic survival model in which the combination significantly prolonged survival compared with the single agents. Importantly, LAM-003 exhibited equipotent activity against FLT3 inhibitor-resistant mutants of FLT3, such as D835 or F691, in cytotoxic and FLT3 degradation assays. LAM-003 also retained potency in AML cells grown in stromal-conditioned media that were resistant to FLT3 inhibitors. Lastly, a genome-wide CRISPR screen revealed epigenetic regulators, including KDM6A, as determinants of LAM-003 sensitivity in AML cell lines, leading to the discovery of synergy with an EZH2 inhibitor. Collectively, these preclinical findings support the use of LAM-003 in FLT3-ITD patients with AML who no longer respond to FLT3 inhibitor therapy either as a single agent or in combination with drugs known to be active in AML.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm/genetics ; Drug Synergism ; Epigenesis, Genetic ; Gene Duplication ; Gene Expression Regulation, Leukemic/drug effects ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Mice ; Mutation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; fms-Like Tyrosine Kinase 3/genetics
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors ; FLT3 protein, human (EC 2.7.10.1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1)
    Language English
    Publishing date 2019-11-14
    Publishing country United States
    Document type Journal Article ; 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.2019001068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Gene patents.

    Rothberg, J M

    Nature

    1992  Volume 356, Issue 6372, Page(s) 738

    MeSH term(s) Genes ; Patents as Topic
    Language English
    Publishing date 1992-04-30
    Publishing country England
    Document type Letter
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/356738d0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Some thoughts on health promotion in the United States Army.

    Rothberg, J M

    Military medicine

    1989  Volume 154, Issue 9, Page(s) 457–461

    MeSH term(s) Health Promotion/legislation & jurisprudence ; Health Promotion/trends ; Humans ; Military Medicine ; United States
    Language English
    Publishing date 1989-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 391061-1
    ISSN 1930-613X ; 0026-4075
    ISSN (online) 1930-613X
    ISSN 0026-4075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Assessment of Brain Injury Using Portable, Low-Field Magnetic Resonance Imaging at the Bedside of Critically Ill Patients.

    Sheth, Kevin N / Mazurek, Mercy H / Yuen, Matthew M / Cahn, Bradley A / Shah, Jill T / Ward, Adrienne / Kim, Jennifer A / Gilmore, Emily J / Falcone, Guido J / Petersen, Nils / Gobeske, Kevin T / Kaddouh, Firas / Hwang, David Y / Schindler, Joseph / Sansing, Lauren / Matouk, Charles / Rothberg, Jonathan / Sze, Gordon / Siner, Jonathan /
    Rosen, Matthew S / Spudich, Serena / Kimberly, W Taylor

    JAMA neurology

    2020  

    Abstract: Importance: Neuroimaging is a key step in the clinical evaluation of brain injury. Conventional magnetic resonance imaging (MRI) systems operate at high-strength magnetic fields (1.5-3 T) that require strict, access-controlled environments. Limited ... ...

    Abstract Importance: Neuroimaging is a key step in the clinical evaluation of brain injury. Conventional magnetic resonance imaging (MRI) systems operate at high-strength magnetic fields (1.5-3 T) that require strict, access-controlled environments. Limited access to timely neuroimaging remains a key structural barrier to effectively monitor the occurrence and progression of neurological injury in intensive care settings. Recent advances in low-field MRI technology have allowed for the acquisition of clinically meaningful imaging outside of radiology suites and in the presence of ferromagnetic materials at the bedside.
    Objective: To perform an assessment of brain injury in critically ill patients in intensive care unit settings, using a portable, low-field MRI device at the bedside.
    Design, setting, and participants: This was a prospective, single-center cohort study of 50 patients admitted to the neuroscience or coronavirus disease 2019 (COVID-19) intensive care units at Yale New Haven Hospital in New Haven, Connecticut, from October 30, 2019, to May 20, 2020. Patients were eligible if they presented with neurological injury or alteration, no contraindications for conventional MRI, and a body habitus not exceeding the scanner's 30-cm vertical opening. Diagnosis of COVID-19 was determined by positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction nasopharyngeal swab result.
    Exposures: Portable MRI in an intensive care unit room.
    Main outcomes and measures: Demographic, clinical, radiological, and treatment data were collected and analyzed. Brain imaging findings are described.
    Results: Point-of-care MRI examinations were performed on 50 patients (16 women [32%]; mean [SD] age, 59 [12] years [range, 20-89 years]). Patients presented with ischemic stroke (n = 9), hemorrhagic stroke (n = 12), subarachnoid hemorrhage (n = 2), traumatic brain injury (n = 3), brain tumor (n = 4), and COVID-19 with altered mental status (n = 20). Examinations were acquired at a median of 5 (range, 0-37) days after intensive care unit admission. Diagnostic-grade T1-weighted, T2-weighted, T2 fluid-attenuated inversion recovery, and diffusion-weighted imaging sequences were obtained for 37, 48, 45, and 32 patients, respectively. Neuroimaging findings were detected in 29 of 30 patients who did not have COVID-19 (97%), and 8 of 20 patients with COVID-19 (40%) demonstrated abnormalities. There were no adverse events or complications during deployment of the portable MRI or scanning in an intensive care unit room.
    Conclusions and relevance: This single-center series of patients with critical illness in an intensive care setting demonstrated the feasibility of low-field, portable MRI. These findings demonstrate the potential role of portable MRI to obtain neuroimaging in complex clinical care settings.
    Keywords covid19
    Language English
    Publishing date 2020-09-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2702023-X
    ISSN 2168-6157 ; 2168-6149
    ISSN (online) 2168-6157
    ISSN 2168-6149
    DOI 10.1001/jamaneurol.2020.3263
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma.

    Gayle, Sophia / Landrette, Sean / Beeharry, Neil / Conrad, Chris / Hernandez, Marylens / Beckett, Paul / Ferguson, Shawn M / Mandelkern, Talya / Zheng, Meiling / Xu, Tian / Rothberg, Jonathan / Lichenstein, Henri

    Blood

    2017  Volume 129, Issue 13, Page(s) 1768–1778

    Abstract: We identified apilimod as an antiproliferative compound by high-throughput screening of clinical-stage drugs. Apilimod exhibits exquisite specificity for phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) lipid kinase and has selective cytotoxic ... ...

    Abstract We identified apilimod as an antiproliferative compound by high-throughput screening of clinical-stage drugs. Apilimod exhibits exquisite specificity for phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) lipid kinase and has selective cytotoxic activity in B-cell non-Hodgkin lymphoma (B-NHL) compared with normal cells. Apilimod displays nanomolar activity in vitro, and in vivo studies demonstrate single-agent efficacy as well as synergy with approved B-NHL drugs. Using biochemical and knockdown approaches, and discovery of a kinase domain mutation conferring resistance, we demonstrate that apilimod-mediated cytotoxicity is driven by PIKfyve inhibition. Furthermore, a critical role for lysosome dysfunction as a major factor contributing to apilimod's cytotoxicity is supported by a genome-wide CRISPR screen. In the screen,
    MeSH term(s) Antineoplastic Agents ; Clustered Regularly Interspaced Short Palindromic Repeats ; Drug Evaluation, Preclinical/methods ; Endosomes/drug effects ; Endosomes/genetics ; High-Throughput Screening Assays ; Humans ; Hydrazones ; Lymphoma, B-Cell/drug therapy ; Lysosomes/drug effects ; Lysosomes/genetics ; Morpholines/therapeutic use ; Phosphatidylinositol 3-Kinases ; Phosphoinositide-3 Kinase Inhibitors ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines ; Triazines/therapeutic use
    Chemical Substances Antineoplastic Agents ; Hydrazones ; Morpholines ; Phosphoinositide-3 Kinase Inhibitors ; Protein Kinase Inhibitors ; Pyrimidines ; Triazines ; PIKFYVE protein, human (EC 2.7.1.137) ; apilimod (GFW2K84S4L)
    Language English
    Publishing date 2017-01-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2016-09-736892
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: B-cell non-Hodgkin lymphoma: Selective vulnerability to PIKFYVE inhibition.

    Gayle, Sophia / Landrette, Sean / Beeharry, Neil / Conrad, Chris / Hernandez, Marylens / Beckett, Paul / Ferguson, Shawn M / Xu, Tian / Rothberg, Jonathan / Lichenstein, Henri

    Autophagy

    2017  Volume 13, Issue 6, Page(s) 1082–1083

    Abstract: We identified the PIKFYVE inhibitor apilimod as a potent and selective cytotoxic agent against B-cell non-Hodgkin lymphoma (B-NHL). Our data robustly establish PIKFYVE as the target through which apilimod kills B-NHL cells and show that apilimod-induced ... ...

    Abstract We identified the PIKFYVE inhibitor apilimod as a potent and selective cytotoxic agent against B-cell non-Hodgkin lymphoma (B-NHL). Our data robustly establish PIKFYVE as the target through which apilimod kills B-NHL cells and show that apilimod-induced death in B-NHL is mediated by broad disruption of lysosome homeostasis characterized by lysosomal swelling, TFEB nuclear translocation, impaired maturation of lysosomal enzymes and incomplete autophagosome clearance. Furthermore, through genome-wide CRISPR knockout screening, we identified specific lysosomal genes (TFEB, CLCN7, OSTM1 and SNX10) as critical determinants of apilimod-induced cytotoxicity. Together these data highlight disruption of lysosome homeostasis through PIKFYVE inhibition as a novel anticancer mechanism in B-NHL and potentially other cancers.
    Language English
    Publishing date 2017-06-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2017.1304871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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