tbuckley/cabot-search huggingface dataset:
Empirical Antifungal Therapy in Critically Ill Patients With Sepsis
Authors: Trishul Siddharthan, Petros C. Karakousis, William Checkley
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Early childhood development coming of age: science through the life course
Authors: Maureen M Black, Susan P Walker, Lia C H Fernald, Christopher T Andersen, Ann M DiGirolamo, Chunling Lu, Dana C McCoy, Günther Fink, Yusra R Shawar, Jeremy Shiffman, Amanda E Devercelli, Quentin T Wodon, Emily Vargas-Barón, Sally Grantham-McGregor
Journal: The Lancet (2016)
The Level of Minimal Residual Disease in Primitive Progenitor Cells from CML Patients after Allogeneic Stem Cell Transplantation Is Higher Than after Treatment with Tyrosine Kinase Inhibitors.
Authors: Agnes S. M. Yong, Keyvan Keyvanfar, Rhoda Eniafe, Bipin N. Savani, Katayoun Rezvani, Aarthi Shenoy, Eleftheria K. Koklanaris, Laura Musse, Theresa Donohue, Quan Le, John M. Goldman, A. John Barrett
Journal: Blood (2008)
FoxO1 and FoxM1 Transcription Factors Have Antagonistic Functions in Neonatal Cardiomyocyte Cell-Cycle Withdrawal and <i>IGF1</i> Gene Regulation
Authors: Arunima Sengupta, Vladimir V. Kalinichenko, Katherine E. Yutzey
Journal: Circulation Research (2012)

Rationale: In the mammalian heart, cardiomyocytes withdraw from the cell cycle and initiate hypertrophic growth soon after birth, but the transcriptional regulatory mechanisms that control these neonatal transitions are not well-defined. Objective: Forkhead family transcription factors have been implicated as positive (forkhead box [Fox] transcription factor M1) and negative (FoxO1 and FoxO3) regulators of cardiomyocyte proliferation prenatally, but their regulatory interactions and functions in neonatal cell-cycle withdrawal have not been reported previously. Potential regulators of Fox activity, including the metabolic indicator AMP-activated protein kinase (AMPK), and Fox transcriptional targets ( p21 , p27 , insulin-like growth factor 1 [ IGF1 ]) also were examined. Methods and Results: In cultured neonatal rat cardiomyocytes, AMPK activates FoxOs, and AMPK inhibition is sufficient to induce cell proliferation. In vivo, combined loss of FoxO1 and FoxO3 specifically in cardiomyocytes leads to delayed cell-cycle withdrawal and increased expression of IGF1 and FoxM1 . Conversely, cardiomyocyte-specific loss of FoxM1 results in decreased neonatal cardiomyocyte cell proliferation, decreased expression of IGF1 , and increased expression of cell-cycle inhibitors p21 and p27 . IGF1 is a direct downstream target of cardiac Fox transcription factors, which is negatively regulated by FoxOs and positively regulated by FoxM1, dependent on AMPK activation status. Conclusions: These data support a regulatory mechanism whereby the balance of FoxO and FoxM1 transcription factors integrates metabolic status, mediated by AMPK, and cell-cycle regulation, through competitive regulation of target genes, including IGF1 , in neonatal cardiomyocytes.
Two doses of NGR-hTNF combined with capecitabine/oxaliplatin (XELOX) in colorectal cancer (CRC) patients failing standard regimens: A phase II study.
Authors: M. Di Benedetto, E. Bennicelli, V. Andretta, A. Pessino, A. Guglielmi, M. S. Sciallero, A. F. Sobrero, G. Fornarini, A. Lambiase, C. Bordignon
Journal: Journal of Clinical Oncology (2010)

e14077 Background: NGR-hTNF consists of tumour necrosis factor (TNF) fused to the tumour homing peptide (NGR), which selectively binds an aminopeptidase N expressed on tumour blood vessels. Preclinically, NGR-hTNF showed a biphasic dose-response curve. Phase I trials previously selected 0.8 μg/m2 and 45 μg/m2 as optimal-biological and maximum-tolerated dose, respectively. Methods: Two sequential cohorts of 12 CRC patients (pts) failing standard therapies were planned to receive NGR-hTNF given at 0.8 μg/m2 (LD) or at 45 μg/m2 (HD) as 1 hour infusion every 3 weeks (q3w). XELOX included capecitabine 825 mg/m2 twice daily for 14 days and oxaliplatin 100 mg/m2 q3w. Safety was the primary aim of the study (< 2/12 pts with grade 3-4 NGR-hTNF-related toxicity). Results: 12 pts were enrolled in the LD cohort and 12 pts in the HD cohort. All but 2 pts had previously received chemotherapy, whereas 9 pts in LD and 10 pts in HD were pretreated also with biologicals. The median number of prior regimens was 3 in LD and 2 in HD. 44 and 35 cycles were delivered in LD and HD, respectively. The combination was well tolerated: no grade 3-4 NGR-hTNF-related toxicities were noted in both cohorts. Most related toxicities were grade 1 to 2 chills experienced by 10 pts during 19 cycles in LD and by 7 pts over 14 cycles in HD. In the LD cohort, one pt (8%) had a partial response and 5 pts (42%) had stable disease for a median duration of 5.0 months (range, 3.0–5.5). In the HD cohort, 4 pts (33%) had stable disease for a median time of 4.1 months (range, 3.0–6.1). For the whole study population, the 3- and 6-month progression-free survival (PFS) rates were 48% (95% CI, 28–69) and 38% (15– 65), respectively. Two pts in the LD cohort experienced PFS times longer than the PFS of prior therapy lines. Conclusions: Both NGR-hTNF doses were safely administered in combination with XELOX in heavily pretreated CRC pts. A hint of activity was apparent with LD NGR-hTNF. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MolMed
472P Predictive and prognostic value of de novo MET expression in patients with advanced non-small cell lung cancer
Authors: A. Li, Y.F. Niu, J.J. Yang, C.X. Zhang, Q. Zhou, J. Su, Z. Xie, N.-N. Lou, Z. Wen-Zhao, H.-Y. Tu, N. Zhao, Y.-L. Wu
Journal: Annals of Oncology (2015)
Final analysis of a randomized study on the value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high risk myelodysplastic syndromes and elderly AML
Authors: G Ossenkoppele, W Graveland, P Sonneveld, S Daenen, D Biesma, L Verdonck, M Schaafsma, P Westveer, G Peters, P Noordhuis, P Muus, D Selleslag, B van der Holt, Michel Delforge, B Lowenberg, Gregor Verhoef
Journal: Blood (2002)
‘Dual’ peptidyl-oligonucleotide conjugates: Role of conformational flexibility in catalytic cleavage of RNA
Authors: Yaroslav Staroseletz, Aled Williams, Kepa K. Burusco, Irfan Alibay, Valentin V. Vlassov, Marina A. Zenkova, Elena V. Bichenkova
Journal: Biomaterials (2016)

Traditional therapeutic interventions against abnormal gene expression in disease states at the level of expressed proteins are becoming increasingly difficult due to poor selectivity, off-target effects and associated toxicity. Upstream catalytic targeting of specific RNA sequences offers an alternative platform for drug discovery to achieve more potent and selective treatment through antisense interference with disease-relevant RNAs. We report a novel class of catalytic biomaterials, comprising amphipathic RNA-cleaving peptides placed between two RNA recognition motifs, here demonstrated to target the TΨC loop and 3′- acceptor stem of tRNAPhe. These unique peptidyl-oligonucleotide 'dual' conjugates (DCs) were created by phosphoramidate or thiol-maleimide conjugation chemistry of a TΨC-targeting oligonucleotide to the N-terminus of the amphipathic peptide sequence, followed by amide coupling of a 3′-acceptor stem-targeting oligonucleotide to the free C-terminal carboxylic acid functionality of the same peptide. Hybridization of the DCs bearing two spatially-separated recognition motifs with the target tRNAPhe placed the peptide adjacent to a single-stranded RNA region and promoted cleavage within the 'action radius' of the catalytic peptide. Up to 100% cleavage of the target tRNAPhe was achieved by the best candidate (i.e. DC6) within 4 h, when conformational flexibility was introduced into the linker regions between the peptide and oligonucleotide components. This study provides the strong position for future development of highly selective RNA-targeting agents that can potentially be used for disease-selective treatment at the level of messenger, micro, and genomic viral RNA.
Comparison of the Villalta Post Thrombotic Syndrome (PTS) Score in the Ipsilateral Versus Contralateral Leg After a First Unprovoked Deep Vein Thrombosis (DVT): Results From the REVERSE Study
Authors: Jean-Philippe Galanaud, Susan R. Kahn, Michael Kovacs, Christina Holcroft, Marisol Betancourt, Philip S Wells, David Anderson, Isabelle Chagnon, Gregoire Le Gal, Susan Solymoss, Mark A. Crowther, Arnaud Perrier, Richard H. White, Linda M Vickars, Tim Ramsay, Marc Rodger
Journal: Blood (2011)
Pembrolizumab (MK-3475) plus low-dose ipilimumab (IPI) in patients (pts) with advanced melanoma (MEL) or renal cell carcinoma (RCC): Data from the KEYNOTE-029 phase 1 study.
Authors: Michael B. Atkins, Toni K. Choueiri, F. Stephen Hodi, John A. Thompson, Wen-Jen Hwu, David F. McDermott, Melissa Brookes, Alessandra Tosolini, Scot Ebbinghaus, Zijiang Yang, Christine K. Gause, Rodolfo F. Perini, Antoni Ribas
Journal: Journal of Clinical Oncology (2015)

3009 Background: Pembrolizumab is a potent, highly selective, humanized monoclonal antibody against PD-1 that has shown robust antitumor activity against several advanced malignancies. In phase 1 testing, combination therapy with the anti–PD-1 antibody nivolumab and full-dose IPI (3 mg/kg) was seemingly associated with improved response rates but also increased toxicities (NEJM 2013;369:122-33). Here, we report the phase 1 data of concurrent administration of pembrolizumab and low-dose IPI in pts with advanced MEL or RCC. Methods: KEYNOTE-029 (NCT02089685) is a phase 1/2 study of pembrolizumab plus IPI or pegylated interferon alfa-2b (PEG-IFN). Assessment of the safety and tolerability of pembrolizumab plus PEG-IFN is ongoing. Safety and tolerability of pembrolizumab 2 mg/kg plus low-dose IPI 1 mg/kg every 3 weeks (Q3W) for 4 doses, followed by pembrolizumab 2 mg/kg Q3W for up to 2 years, were assessed. Dose confirmation continued until 18 pts completed the 6-wk observation period (Cycle 1). DLTs were evaluated in pts who completed the first cycle of combination therapy or who discontinued due to a treatment-related AE. The dose would be considered tolerable if ≤6 pts experienced DLTs. Toxicities were graded by CTCAE v4.0. Response is assessed at wk 12, every 6 wk thereafter until wk 30, and every 12 wk thereafter. Results: DLTs were observed in 6 of 19 evaluable pts (2 of 9 RCC pts, 4 of 10 MEL pts). All DLTs were of grade 3 severity. Two pts experienced 2 DLTs each: elevation of pancreatic enzymes and hyperthyroidism in 1 patient and lipase elevation and pneumonitis in another patient. The remaining DLTs were ALT/AST elevation (n = 2), colitis (n = 1), and uveitis (n = 1). Responses have been observed in MEL and RCC pts. Additional safety and preliminary efficacy data will be available for presentation. Conclusions: Pembrolizumab and low-dose IPI combination therapy was considered to have an acceptable safety profile in this initial safety run-in period. Based on these results, we have initiated a protocol-specified, single-arm expansion cohort to further evaluate the safety, tolerability, and preliminary efficacy of this combination in advanced MEL pts. Clinical trial information: NCT02089685.
Programming of donor T cells using allogeneic δ-like ligand 4–positive dendritic cells to reduce GVHD in mice
Authors: Kazuhiro Mochizuki, Lijun Meng, Izumi Mochizuki, Qing Tong, Shan He, Yongnian Liu, Janaki Purushe, Henry Fung, M. Raza Zaidi, Yanyun Zhang, Ran Reshef, Bruce R. Blazar, Hideo Yagita, Shin Mineishi, Yi Zhang
Journal: Blood (2016)
Multicentric ALL-BFM 2000 Trial: Evaluation of the quality of cranial radiotherapy in childhood acute lymphatic leukemia
Authors: A. Warszawski, B. Buerger, J. H. Karstens, R. Baumann, M. Schrappe
Journal: Journal of Clinical Oncology (2004)

8545 Background: Despite controversial discussions, cranial radiotherapy is an important part of ALL treatment in children with risk factors. The complete coverage of the brain and the meninges is of outstanding importance for patients' outcome. QA of cranial radiotherapy of the prospective randomized ALL-BFM 2000 trail regarding the quality of used radiation, target volume, fraction size and dose. Methods: From 7/2000 to 6/2002 in 251 children with risk factors, age 1–16 years (median 6.6 yr.), cranial radiotherapy was indicated according to the protocol. They were treated in 104 institutions. These institutions were asked to send voluntarily simulator and field verification films, treatment protocols and plans of all children randomized in the trial. The quality of used radiation, target volume, fraction size and dose were reviewed. The deviation was defined as minor or major deviation from protocol guidelines using the criteria of the QA review of the POG 9404 trial (Halperin EC et al. IJROBP 2002). Results: Up to now we received treatment protocols, simulator or verification films of 118/251 children (47%) treated in 47 institutions. Of these 118 children 76 received a cranial radiotherapy (65 prophylactic, 11 therapeutic). Total doses of 12 or 18 Gy, respectively, were delivered in all cases according to the protocol. We found in 3.9% of cases minor deviations in the applied single doses. In all 76 children a thermoplastic mask for fixation was used. In all but 2 patients a photon beam with a nominal energy of 5 or 6 MV was used. The target volume was covered in 13.7% with minor quality deviations in 15.1% with major deviations. As a result, in these cases underdosages of the cribriform plate, the optical nerve region and/or the spinal segments occurred. Conclusion: The presented data showed incidence of insufficient target volume coverage in cranial radiotherapy of children with ALL despite clearly written protocol guidelines. Therefore QA of cranial radiotherapy is important and may result in better treatment practice and outcome. This analysis continues to lend credence to efforts related to QA for radiotherapy in cooperative group protocols. No significant financial relationships to disclose.
Multiplex Genome Editing As a Platform for “Off-the-Shelf” Adoptive CAR T-Cell Immunotherapies
Authors: Sophie Derniame, Hong Zhan, Laurent Poirot, Cecile Schiffer-Mannioui, Roman Galetto, Marine Beurdeley, Stephan Reynier, Sylvain Arnould, Waseem Qasim, Julianne Smith
Journal: Blood (2014)
Ten-year incidence of contact dermatitis in a prospective cohort of healthcare workers in Trieste hospitals (North East of Italy) 2004-2013
Authors: F. Larese Filon, S. Plazzotta, F. Rui, M. Mauro, P. De Michieli, C. Negro
Journal: British Journal of Dermatology (2016)

The incidence of OCD (occupational contact dermatitis) in different European Countries and USA ranges between 0.5 and 1.9 cases per 1000 workers per year. 1,2,3 OCD is lowering in the last 10-15 years, with incidence rate that varies between 1.2 to 0.56 cases per 1000 person-years from 1993 to 1996 in Germany 1,3 and from 0.29 to 0.1 cases per 1000 from 1997 to 2008 in a Czech study.4

Incidence of notified occupational skin diseases for health care workers (HCWs) was 3.1 cases per 1000 workers per year in USA, 1.5 in Bavaria, 1.5 in Denmark (only nurses), 0.4 in Northem Bavaria and 0.1-0.29 in Czech Republic.4

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Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With <i>ALK</i>-Positive Non–Small-Cell Lung Cancer
Authors: Shirish M. Gadgeel, Alice T. Shaw, Ramaswamy Govindan, Leena Gandhi, Mark A. Socinski, D. Ross Camidge, Luigi De Petris, Dong-Wan Kim, Alberto Chiappori, Denis L. Moro-Sibilot, Michael Duruisseaux, Lucio Crino, Tommaso De Pas, Eric Dansin, Antje Tessmer, James Chih-Hsin Yang, Ji-Youn Han, Walter Bordogna, Sophie Golding, Ali Zeaiter, Sai-Hong Ignatius Ou
Journal: Journal of Clinical Oncology (2016)

Purpose Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results One hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.
Ambulatory Oncology Operations: Strategies to Alleviate Complexity
Authors: Chadi Nabhan, Sandeep Parsad
Journal: Journal of the National Comprehensive Cancer Network (2016)

Although 1.8 million new cancer cases are detected annually, most patients who are diagnosed remain alive at 5 years. 1 Factors contributing to this success include advancements in science, better supportive care, and technological progress. 2Addressing the needs of patients with cancer has become a major operational challenge as more cancers are detected earlier and more patients are living longer.Patients receive complex, multimodality therapy in a variety of settings, including the integration of various disciplines.Coordination of care for newly diagnosed patients-often an urgent scenario requiring rapid diagnostic studies and treatment initiation-is essential for success.Care for survivors also requires coordination, with similar implications on cancer care operations.Although the increase in the number of patients with cancer and the associated revenues from these cases have led academic and community institutions to declare cancer as the premier service line, delivering cancer care efficiently and effectively remains an operational contest with no easy answers.This challenge is increasingly obvious as cancer care delivery is shifted to the outpatient arena and as the number of oncologists in the United States is projected to fall short of increased demand. 3
B Cell Receptor (BCR) Signal Pathways Confer Microenvironment-Mediated Drug Resistance and Are Promising Therapeutic Targets for B Cell Lymphomas
Authors: Jiangchuan Tao, Tint Lwin, Xiaohong Zhao, Ling Zhang, Lynn Moscinski, Eduardo M. Sotomayor, William S. Dalton, Jianguo Tao
Journal: Blood (2012)
Haploidentical Transplantation Using T-Cell Replete Peripheral Blood Stem Cells and Myeloablative Conditioning in Patients with High-Risk Hematologic Malignancies Who Lack Conventional Donors Is Well Tolerated and Produces Excellent Relapse-Free Survival: Results of A Prospective Phase II Trial
Authors: Connie A. Sizemore, Asad Bashey, Melissa Sanacore, Karen Manion, H. Kent Holland, Lawrence E. Morris, Stacey Brown, Xu Zhang, Scott R. Solomon
Journal: Blood (2011)
Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling
Authors: David A. Ewald, Shinji Noda, Margeaux Oliva, Thomas Litman, Saeko Nakajima, Xuan Li, Hui Xu, Christopher T. Workman, Peter Scheipers, Naila Svitacheva, Tord Labuda, James G. Krueger, Mayte Suárez-Fariñas, Kenji Kabashima, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2016)