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  1. Article ; Online: Novel Drug Treatments of Progressive Radioiodine-Refractory Differentiated Thyroid Cancer.

    Weitzman, Steven P / Sherman, Steven I

    Endocrinology and metabolism clinics of North America

    2018  Volume 48, Issue 1, Page(s) 253–268

    Abstract: Systemic therapy options have emerged for treatment of progressive, radioiodine-refractory differentiated thyroid carcinoma. Approved therapies that target tumor angiogenesis, lenvatinib and sorafenib, improve progression-free survival and, in an older ... ...

    Abstract Systemic therapy options have emerged for treatment of progressive, radioiodine-refractory differentiated thyroid carcinoma. Approved therapies that target tumor angiogenesis, lenvatinib and sorafenib, improve progression-free survival and, in an older subset, lenvatinib can prolong overall survival. Treatments based on targeting specific somatic genetic alterations are also available, which potentially also may prolong progression-free survival but are not yet approved for use by the Food and Drug Administration for this specific disease. More novel approaches that may benefit select patients include resensitization therapies that allow further radioiodine utilization and new immunotherapy concepts.
    MeSH term(s) Disease Progression ; Genetic Therapy/methods ; Humans ; Immunotherapy/methods ; Protein Kinase Inhibitors/therapeutic use ; Thyroid Neoplasms/drug therapy ; Thyroid Neoplasms/therapy
    Chemical Substances Protein Kinase Inhibitors
    Language English
    Publishing date 2018-12-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 92116-6
    ISSN 1558-4410 ; 0889-8529
    ISSN (online) 1558-4410
    ISSN 0889-8529
    DOI 10.1016/j.ecl.2018.10.009
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  2. Article ; Online: Acupuncture in cancer care: recommendations for safe practice (peer-reviewed expert opinion).

    de Valois, Beverley / Young, Teresa / Zollman, Catherine / Appleyard, Ian / Ben-Arye, Eran / Cummings, Mike / Green, Ruth / Hoffman, Caroline / Lacey, Judith / Moir, Felicity / Peckham, Rachel / Stringer, Jacqui / Veleber, Susan / Weitzman, Matthew / Wode, Kathrin

    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

    2024  Volume 32, Issue 4, Page(s) 229

    Abstract: Background: Up-to-date recommendations for the safe practice of acupuncture in integrative oncology are overdue with new cancer treatments and an increase in survivors with late effects of disease; 17 years have elapsed since Filshie and Hester's 2006 ... ...

    Abstract Background: Up-to-date recommendations for the safe practice of acupuncture in integrative oncology are overdue with new cancer treatments and an increase in survivors with late effects of disease; 17 years have elapsed since Filshie and Hester's 2006 guidelines. During 2022/2023 an expert panel assembled to produce updated recommendations aiming to facilitate safe and appropriate care by acupuncturists working with people with cancer.
    Methods: A core development team comprising three integrative oncology professionals comprehensively updated pre-existing unpublished recommendations. Twelve invited international experts (senior acupuncturists with and without experience of working in oncology settings, oncologists, physicians and nurses trained in integrative oncology, researchers, academics, and professional body representatives) reviewed the recommendations. In multiple iterations, the core team harmonised comments for final ratification. To aid dissemination and uptake the panel represents national and international integrative oncology associations and major cancer treatment centres in Europe, USA, Australia, and the Middle East.
    Results: These recommendations facilitate safe care by articulating contra-indications, cautions, and risks for patients both on and off treatment (surgery, SACT, radiotherapy). Situations where acupuncture may be contra-indicated or practices need adapting are identified. "Red and Amber Flags" highlight where urgent referral is essential.
    Conclusion: These are the first international, multidisciplinary peer-reviewed recommendations for safe acupuncture practice in integrative oncology. Concerns about safety remain a significant barrier to appropriate referral from oncology teams, to use by acupuncturists and to uptake by patients. Disseminating trustworthy, widely accessible guidance should facilitate informed, confident practice of acupuncture in and outside of oncology healthcare settings.
    MeSH term(s) Humans ; Expert Testimony ; Acupuncture Therapy ; Acupuncture ; Neoplasms/therapy ; Medical Oncology
    Language English
    Publishing date 2024-03-14
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1134446-5
    ISSN 1433-7339 ; 0941-4355
    ISSN (online) 1433-7339
    ISSN 0941-4355
    DOI 10.1007/s00520-024-08386-6
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  3. Article ; Online: Defining Developmental-Behavioral Pediatrics.

    Weitzman, Carol C / Baum, Rebecca A / Fussell, Jill / Korb, Damon / Leslie, Laurel K / Spinks-Franklin, Adiaha I A / Voigt, Robert G

    Pediatrics

    2022  Volume 149, Issue 4

    Abstract: There is an insufficient number of specialty developmental-behavioral pediatrics (DBP) physicians, despite nearly 25% of children and adolescents having a developmental, learning, behavioral, or emotional problem. In the nearly 20 years since becoming a ... ...

    Abstract There is an insufficient number of specialty developmental-behavioral pediatrics (DBP) physicians, despite nearly 25% of children and adolescents having a developmental, learning, behavioral, or emotional problem. In the nearly 20 years since becoming a board-certified subspecialty, the definition of DBP clinical practice remains somewhat unclear. This lack of clarity likely contributes to recruitment challenges and workforce issues, and limited visibility of DBP among parents, other professionals, payors, and administrators. Defining DBP is therefore an important step in the survival and growth of the field. In this paper, we describe the methodology used to develop this definition along with the origins of DBP, the persistent challenges to defining its scope, what training in DBP involves, and what distinguishes DBP from other overlapping fields of medicine. We propose the following definition of DBP: developmental-behavioral pediatrics (DBP) is a board-certified, medical subspecialty that cares for children with complex and severe DBP problems by recognizing the multifaceted influences on the development and behavior of children and addressing them through systems-based practice and a neurodevelopmental, strength-based approach that optimizes functioning. Developmental behavioral pediatricians care for children from birth through young adulthood along a continuum including those suspected of, at risk for, or known to have developmental and behavioral disorders.
    MeSH term(s) Adolescent ; Adult ; Certification ; Child ; Humans ; Mental Disorders ; Parents ; Pediatrics ; Young Adult
    Language English
    Publishing date 2022-03-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207677-9
    ISSN 1098-4275 ; 0031-4005
    ISSN (online) 1098-4275
    ISSN 0031-4005
    DOI 10.1542/peds.2021-054771
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  4. Article ; Online: DRUMMER-rapid detection of RNA modifications through comparative nanopore sequencing.

    Abebe, Jonathan S / Price, Alexander M / Hayer, Katharina E / Mohr, Ian / Weitzman, Matthew D / Wilson, Angus C / Depledge, Daniel P

    Bioinformatics (Oxford, England)

    2022  Volume 38, Issue 11, Page(s) 3113–3115

    Abstract: Motivation: The chemical modification of ribonucleotides regulates the structure, stability and interactions of RNAs. Profiling of these modifications using short-read (Illumina) sequencing techniques provides high sensitivity but low-to-medium ... ...

    Abstract Motivation: The chemical modification of ribonucleotides regulates the structure, stability and interactions of RNAs. Profiling of these modifications using short-read (Illumina) sequencing techniques provides high sensitivity but low-to-medium resolution i.e. modifications cannot be assigned to specific transcript isoforms in regions of sequence overlap. An alternative strategy uses current fluctuations in nanopore-based long read direct RNA sequencing (DRS) to infer the location and identity of nucleotides that differ between two experimental conditions. While highly sensitive, these signal-level analyses require high-quality transcriptome annotations and thus are best suited to the study of model organisms. By contrast, the detection of RNA modifications in microbial organisms which typically have no or low-quality annotations requires an alternative strategy. Here, we demonstrate that signal fluctuations directly influence error rates during base-calling and thus provides an alternative approach for identifying modified nucleotides.
    Results: DRUMMER (Detection of Ribonucleic acid Modifications Manifested in Error Rates) (i) utilizes a range of statistical tests and background noise correction to identify modified nucleotides with high confidence, (ii) operates with similar sensitivity to signal-level analysis approaches and (iii) correlates very well with orthogonal approaches. Using well-characterized DRS datasets supported by independent meRIP-Seq and miCLIP-Seq datasets we demonstrate that DRUMMER operates with high sensitivity and specificity.
    Availability and implementation: DRUMMER is written in Python 3 and is available as open source in the GitHub repository: https://github.com/DepledgeLab/DRUMMER.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Nanopore Sequencing ; Software ; Sequence Analysis, RNA/methods ; High-Throughput Nucleotide Sequencing/methods ; RNA/chemistry ; Nucleotides
    Chemical Substances RNA (63231-63-0) ; Nucleotides
    Language English
    Publishing date 2022-04-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btac274
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  5. Article ; Online: Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy.

    Villares, Marie / Lourenço, Nelly / Ktorza, Ivan / Berthelet, Jérémy / Panagiotou, Aristeidis / Richard, Aurélie / Amo, Angélique / Koziy, Yulianna / Medjkane, Souhila / Valente, Sergio / Fioravanti, Rossella / Pioche-Durieu, Catherine / Lignière, Laurent / Chevreux, Guillaume / Mai, Antonello / Weitzman, Jonathan B

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2235

    Abstract: Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved ... ...

    Abstract Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved sophisticated strategies to hijack host leukocytes, inducing proliferative and invasive phenotypes characteristic of cell transformation. Intracellular Theileria parasites secrete proteins into the host cell and recruit host proteins to induce oncogenic signaling for parasite survival. It is unknown how Theileria parasites evade host cell defense mechanisms, such as autophagy, to survive within host cells. Here, we show that Theileria annulata parasites sequester the host eIF5A protein to their surface to escape elimination by autophagic processes. We identified a small-molecule compound that reduces parasite load by inducing autophagic flux in host leukocytes, thereby uncoupling Theileria parasite survival from host cell survival. We took a chemical genetics approach to show that this compound induced host autophagy mechanisms and the formation of autophagic structures via AMPK activation and the release of the host protein eIF5A which is sequestered at the parasite surface. The sequestration of host eIF5A to the parasite surface offers a strategy to escape elimination by autophagic mechanisms. These results show how intracellular pathogens can avoid host defense mechanisms and identify a new anti-Theileria drug that induces autophagy to target parasite removal.
    MeSH term(s) Animals ; Cattle ; Theileria/genetics ; Parasites ; Theileriasis/parasitology ; Host-Parasite Interactions/physiology ; Signal Transduction
    Language English
    Publishing date 2024-03-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45022-7
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  6. Article ; Online: Untargeted Metabolomics to Characterize the Urinary Chemical Landscape of E-Cigarette Users.

    Hsiao, Yun-Chung / Matulewicz, Richard S / Sherman, Scott E / Jaspers, Ilona / Weitzman, Michael L / Gordon, Terry / Liu, Chih-Wei / Yang, Yifei / Lu, Kun / Bjurlin, Marc A

    Chemical research in toxicology

    2023  Volume 36, Issue 4, Page(s) 630–642

    Abstract: The health and safety of using e-cigarette products (vaping) have been challenging to assess and further regulate due to their complexity. Inhaled e-cigarette aerosols contain chemicals with under-recognized toxicological profiles, which could influence ... ...

    Abstract The health and safety of using e-cigarette products (vaping) have been challenging to assess and further regulate due to their complexity. Inhaled e-cigarette aerosols contain chemicals with under-recognized toxicological profiles, which could influence endogenous processes once inhaled. We urgently need more understanding on the metabolic effects of e-cigarette exposure and how they compare to combustible cigarettes. To date, the metabolic landscape of inhaled e-cigarette aerosols, including chemicals originated from vaping and perturbed endogenous metabolites in vapers, is poorly characterized. To better understand the metabolic landscape and potential health consequences of vaping, we applied liquid chromatography-mass spectrometry (LC-MS) based nontargeted metabolomics to analyze compounds in the urine of vapers, cigarette smokers, and nonusers. Urine from vapers (
    MeSH term(s) Humans ; Smokers ; Electronic Nicotine Delivery Systems ; Nicotine ; Gas Chromatography-Mass Spectrometry ; Vaping/adverse effects ; Aerosols ; Metabolomics ; Biomarkers, Tumor ; Fatty Acids
    Chemical Substances Nicotine (6M3C89ZY6R) ; Aerosols ; Biomarkers, Tumor ; Fatty Acids
    Language English
    Publishing date 2023-03-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/acs.chemrestox.2c00346
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  7. Article ; Online: A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies.

    Al-Samkari, Hanny / Parnes, Aric D / Goodarzi, Katayoon / Weitzman, James I / Connors, Jean M / Kuter, David J

    Haematologica

    2021  Volume 106, Issue 4, Page(s) 1148–1157

    Abstract: Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy delays, dose reductions, and discontinuation. There is no FDA-approved agent available to manage CIT. This study retrospectively evaluated patients ... ...

    Abstract Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy delays, dose reductions, and discontinuation. There is no FDA-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at 4 U.S. centers. The primary outcome was achievement of a romiplostim response [median on-romiplostim platelet count (Plt) ≥75x109/L and ≥30x109/L above baseline]. Secondary outcomes included time to Plt≥100x109/L and rates of the following: Plt<100x109/L, Plt<75x109/L, Plt<50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of 4 (range, 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays and 89% avoided platelet transfusions. Median per-patient Plt on romiplostim was significantly higher than baseline (116x109/L vs. 60x109/L, P<0.001). Bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays (IRR 3.00, 95% CI 1.30-6.91, P=0.010) or bleeding (IRR 4.84, 95% CI 1.18-19.89, P=0.029). Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with bone marrow involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.
    MeSH term(s) Antineoplastic Agents/adverse effects ; Hematologic Neoplasms/drug therapy ; Humans ; Neoplasms/complications ; Neoplasms/drug therapy ; Receptors, Fc/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Retrospective Studies ; Thrombocytopenia/chemically induced ; Thrombocytopenia/drug therapy ; Thrombopoietin/therapeutic use
    Chemical Substances Antineoplastic Agents ; Receptors, Fc ; Recombinant Fusion Proteins ; Thrombopoietin (9014-42-0) ; romiplostim (GN5XU2DXKV)
    Language English
    Publishing date 2021-04-01
    Publishing country Italy
    Document type Journal Article ; Multicenter Study
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2020.251900
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  8. Article ; Online: A role for surgery in the treatment of relapsed Hodgkin lymphoma.

    Fahy, A S / Kong, I / Weitzman, S / Dix, D / Baruchel, S / Gerstle, J T

    Pediatric blood & cancer

    2018  Volume 66, Issue 1, Page(s) e27402

    Abstract: Treatment of Hodgkin lymphoma (HL) has advanced over time, rendering a fatal disease now largely curable. Multiagent chemotherapy regimens, hematopoietic stem cell transplantation, and radiotherapy are the mainstays of care. Surgical intervention is ... ...

    Abstract Treatment of Hodgkin lymphoma (HL) has advanced over time, rendering a fatal disease now largely curable. Multiagent chemotherapy regimens, hematopoietic stem cell transplantation, and radiotherapy are the mainstays of care. Surgical intervention is rarely indicated other than for biopsy at diagnosis. However, for patients with recurrent relapsed HL isolated to one anatomical location, refractory to all other therapy, there may be a beneficial role for surgical excision. Herein, we report the surgical management of three relapsed patients with stage IVB HL who were refractory to multiple other therapeutic approaches, who all achieved good event-free survival after operative management.
    MeSH term(s) Adolescent ; Child ; Female ; Hodgkin Disease/pathology ; Hodgkin Disease/surgery ; Humans ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/surgery ; Prognosis ; Salvage Therapy ; Surgical Procedures, Operative/methods
    Language English
    Publishing date 2018-10-08
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.27402
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  9. Article ; Online: Barriers and Facilitators of Hepatitis C Care in Persons Coinfected with Human Immunodeficiency Virus.

    Bar, Nir / Bensoussan, Noa / Rabinowich, Liane / Levi, Sharon / Houri, Inbal / Ben-Ami Shor, Dana / Shibolet, Oren / Mor, Orna / Weitzman, Ella / Turner, Dan / Katchman, Helena

    International journal of environmental research and public health

    2022  Volume 19, Issue 22

    Abstract: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are often co-transmitted. Viral coinfection results in worse outcomes. Persons who inject drugs (PWIDs) face barriers to medical treatment, but HCV treatment is indicated and effective even ... ...

    Abstract Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are often co-transmitted. Viral coinfection results in worse outcomes. Persons who inject drugs (PWIDs) face barriers to medical treatment, but HCV treatment is indicated and effective even with ongoing active drug use. We aimed to assess access to HCV care and treatment results in patients coinfected with HIV-HCV. This is a real-world retrospective single-center study of patients followed in the HIV clinic between 2002 and 2018. Linkage to care was defined as achieving care cascade steps: (1) hepatology clinic visit, (2) receiving prescription of anti-HCV treatment, and (3) documentation of sustained virologic response (SVR). Of 1660 patients with HIV, 254 with HIV-HCV coinfection were included. Only 39% of them achieved SVR. The rate limiting step was the engagement into hepatology care. Being a PWID was associated with ~50% reduced odds of achieving study outcomes, active drug use was associated with ~90% reduced odds. Older age was found to facilitate treatment success. Once treated, the rate of SVR was high in all populations. HCV is undertreated in coinfected young PWIDs. Further efforts should be directed to improve access to care in this marginalized population.
    MeSH term(s) Humans ; Coinfection/epidemiology ; Coinfection/drug therapy ; Hepacivirus ; HIV Infections/complications ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Retrospective Studies ; Drug Users ; Antiviral Agents/therapeutic use ; Substance Abuse, Intravenous/drug therapy ; Hepatitis C/complications ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; HIV
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2022-11-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2175195-X
    ISSN 1660-4601 ; 1661-7827
    ISSN (online) 1660-4601
    ISSN 1661-7827
    DOI 10.3390/ijerph192215237
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  10. Article: SUSCEPTIBILITY AND RESISTANCE TO TRYPANOSOME INFECTION : II. THE RELATION OF PHYSICAL ENVIRONMENT TO HOST SUSCEPTIBILITY TO INFECTION.

    Kligler, I J / Weitzman, I

    The Journal of experimental medicine

    2009  Volume 44, Issue 3, Page(s) 409–417

    Language English
    Publishing date 2009-10-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.44.3.409
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