tbuckley/cabot-search huggingface dataset:
Pharmacogenomics: Personalizing palliative pharmacotherapy.
Authors: Caleb Scheckel, Adrijana Kekic, Mark Edwin
Journal: Journal of Clinical Oncology (2019)

126 Background: Pharmacogenomics (PGx) is a developing field in individualized medicine concerned with understanding genetic polymorphisms that may explain inter-individual variation in drug efficacy and toxicity. Understanding these polymorphisms is a key tool in guiding clinician’s selection and dosing of specific medications to optimally manage patient symptoms. Common pharmacogenes that impact analgesic prescribing include: CYP2D6, OPRM1, and COMT; for mood disorders: CYP2C19. This cross-sectional study explored the activity of pharmacogenes of clinical significance in palliative medicine with either Level 1 or 2 evidence. Methods: We performed PGx testing on 50 new referrals to the palliative medicine clinic with an active malignancy. Each patient underwent PGx testing with clinical pharmacist review and interpretation prior to their initial office appointment. Results: In our cohort 54% were men and the mean age was 64.7 (24-87). The average number of medications, medication allergies, and creatinine clearance were 10.5 (1-22), 1.3 (0-13), and 78.4 (31-120), respectively. Among the pharmacogenes impacting opiate and antiemetic prescribing, 14% (7/50) of patients were poor metabolizers of CYP2D6 and 8% (4/50) were rapid or ultra-rapid metabolizers. Another 60% (30/50) showed intermediate metabolism which would impact initial dosing. Poor metabolism of COMT or OPRM1 was seen in 8% (4/50) with another 36% (18/50) demonstrating rapid metabolism. Activity for the pharmacogene CYP2C19, which impacts many psychotropics, revealed 32% (16/50) rapid or ultra-rapid metabolizers and no poor metabolizers. Overall, 66% (33/50) of patients had pharmacogene activity suggestive of significant clinical impact necessitating either drug avoidance due to toxicity risks or substantial dose adjustment to be efficacious. Conclusions: Polymorphisms impacting pharmacotherapy were common in our cohort. Patients with difficult-to-control symptoms or multiple medication toxicities can utilize PGx testing as a guide to symptom relief. As PGx technology becomes readily accessible and economical, opportunities for patients to have precision genomic information guide healthcare decisions is expected to increase.
The Management of Stroke Rehabilitation: A Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline
Authors: James Sall, Blessen C. Eapen, Johanna Elizabeth Tran, Amy O. Bowles, Andrew Bursaw, M. Eric Rodgers
Journal: Annals of Internal Medicine (2019)

In June 2019, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved an update of the joint clinical practice guideline for rehabilitation after stroke. This synopsis summarizes the key recommendations from this guideline.In February 2018, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and stroke survivors and conformed to the National Academy of Medicine (formerly the Institute of Medicine) tenets for trustworthy clinical practice guidelines. The guideline panel identified key questions, systematically searched and evaluated the literature, and developed 2 algorithms and 42 key recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Stroke survivors and their family members were invited to share their perspectives to further inform guideline development.The guideline recommendations provide evidence-based guidance for the rehabilitation care of patients after stroke. The recommendations are applicable to health care providers in both primary care and rehabilitation. Key features of the guideline are recommendations in 6 areas: timing and approach; motor therapy; dysphagia; cognitive, speech, and sensory therapy; mental health therapy; and other functions, such as returning to work and driving.
#SafeSport: safeguarding initiatives at the Youth Olympic Games 2018
Authors: Margo Mountjoy, Tine Vertommen, Kirsty Burrows, Susan Greinig
Journal: British Journal of Sports Medicine (2019)

Little is known about athletes' understanding of safe sport and occurrence of harassment and abuse in elite youth sport.To evaluate the IOC Safe Sport educational experience at the Youth Olympic Games 2018 in Buenos Aires and to ascertain the athletes' (1) understanding of what constitutes harassment and abuse, (2) perception of the occurrence in their sport, and (3) knowledge of where to report.Athletes visiting the IOC Safe Sport Booth answered a survey related to athletes' (1) understanding of harassment and abuse in sport, (2) perception of the occurrence of harassment and abuse in their sport, and (3) knowledge of where to report. Experts and volunteers answered an email survey on their experience.The response rate was 71.8%. When asked to define 'safe sport', the athletes mainly relate the concept to general physical and environmental safety, fair play and clean sport, rather than sport free from harassment and abuse. Almost half (46%) of the athletes expressed surprise by the definition of behaviours of harassment and abuse within sport. When asked if harassment and/or abuse occur in their sport, 47.5% reported 'no' or 'not likely', while 34% stated 'likely' or 'very likely'; 19% were 'unsure'. The majority (63%) of athletes knew where to seek help. Three quarters (71%) of the athletes rated the educational materials as 'good' to 'excellent'. The experts and volunteers believed the intervention would result in change in athletes' awareness, knowledge and behaviour.This multinational cohort of elite youth athletes is not knowledgeable of the concept of harassment and abuse in sport, despite there being a significant perception of occurrence of harassment and abuse in their sports.
Operator Volume to Outcome Relationship in Mitral and Aortic Valve Replacement
Authors: Arash Salemi, Mario Gaudino, Faisal Bakaeen, Jialin Mao, Irbaz Hameed, Faiza M. Khan, Lisa Q. Rong, Matthew Wingo, Leonard N. Girardi, Art Sedrakyan
Journal: Journal of the American College of Cardiology (2019)
The QUAZAR AML-001 Maintenance Trial: Results of a Phase III International, Randomized, Double-Blind, Placebo-Controlled Study of CC-486 (Oral Formulation of Azacitidine) in Patients with Acute Myeloid Leukemia (AML) in First Remission
Authors: Andrew H. Wei, Hartmut Döhner, Christopher Pocock, Pau Montesinos, Boris Afanasyev, Hervé Dombret, Farhad Ravandi, Hamid Sayar, Jun Ho Jang, Kimmo Porkka, Dominik Selleslag, Irwindeep Sandhu, Mehmet Turgut, Valentina Giai, Yishai Ofran, Merih Kizil Cakar, Aida Botelho de Sousa, Justyna Rybka, Chiara Frairia, Lorenza Borin, Germana Beltrami, Jaroslav Cermak, Gert J. Ossenkoppele, Ignazia La Torre, Barry Skikne, Keshava Kumar, Qian Dong, CL Beach, Gail J. Roboz
Journal: Blood (2019)
Neural code: Another breach in the wall?
Authors: Chloé Huetz, Samira Souffi, Victor Adenis, Jean-Marc Edeline
Journal: Behavioral and Brain Sciences (2019)

Abstract Brette presents arguments that query the existence of the neural code. However, he has neglected certain evidence that could be viewed as proof that a neural code operates in the brain. Albeit these proofs show a link between neural activity and cognition, we discuss why they fail to demonstrate the existence of an invariant neural code.
Family Visitation Policies in the ICU and Delirium—Reply
Authors: Regis Goulart Rosa, Maicon Falavigna, Cassiano Teixeira
Journal: JAMA (2019)

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
Timing of adjuvant chemotherapy initiation and colon cancer survival.
Authors: Aaron Gehr, Yan Lu, Bassam Ghabach, Kalyani Narra, Latha Sri Neerukonda, Jolonda Bullock, Rohit P. Ojha
Journal: Journal of Clinical Oncology (2019)

119 Background: The National Quality Forum endorsed initiation of adjuvant chemotherapy within 120 days of diagnosis for stage III colon cancer patients aged &lt; 80 years. Nevertheless, no trials were conducted to establish this 120-day threshold and observational studies used to justify this threshold may be sensitive to recently identified sources of bias. Therefore, we aimed to assess the effect of initiating adjuvant chemotherapy within 120 days on survival among patients with stage III colon cancer. Methods: We used institutional registry data from the JPS Center for Cancer Care (JPS), an accredited Comprehensive Community Cancer Program. Eligible patients were adults aged &lt; 80 years, diagnosed with first primary stage III colon cancer between 2011 and 2015, and received at least part of their first course treatment at JPS. Overall survival was defined as time from cancer diagnosis to death, loss to follow-up, or end of study. We emulated a pragmatic trial and estimated the intention to treat 36-month restricted mean survival difference and 95% confidence limits (CL) for initiating adjuvant chemotherapy within 120 days using a marginal structural model with stabilized inverse probability of treatment weights to reduce confounding bias. Results: Our study population comprised 62 patients, of whom 61% were aged 55 – 64 years, 58% were females, 61% were racial/ethnic minorities, 69% were uninsured, and 61% initiated adjuvant chemotherapy within 120 days after cancer diagnosis. The mean survival after 36 months of follow-up was 31 months (95% CL: 27, 34) for patients who initiated and 31 months (95% CL: 28, 34) for patients who did not initiate adjuvant chemotherapy within 120 days (mean survival difference = -0.10 months, 95% CL: -3.6, 3.4). Conclusions: Our results suggest no meaningful difference in overall survival between initiating or not initiating adjuvant treatment within 120 days of diagnosis for patients with stage III colon cancer, but our estimates are compatible with either a 3-month survival benefit or harm. A larger sample size may provide greater certainty whether the 120-day threshold is a questionable quality measure, as observed in our study.
Direct and indirect economic evaluation of upfront and sequential adjuvant treatment in postmenopausal women with breast cancer based on the BIG 1–98 trial
Authors: C. Skedgel, D. Rayson, T. Younis
Journal: Journal of Clinical Oncology (2009)

6594 Background: The monotherapy arms of the BIG 1–98 trial established the clinical superiority of upfront letrozole (LET) relative to tamoxifen alone (TAM) but direct comparison of sequential TAM-LET, LET-TAM and upfront LET did not establish a clinically superior strategy. We undertook an economic evaluation to identify an economically preferred strategy based on the relative cost-effectiveness (CE) of TAM, LET, TAM-LET, and LET-TAM in terms of cost per quality-adjusted life year gained (QALYG). Methods: A state-transition model was developed to calculate cumulative costs and QALYs over a 25yr horizon for hypothetical cohorts of postmenopausal women with HR+ breast cancer undergoing adjuvant hormonal treatment. As the sequential arms were not directly compared to TAM alone, it was not possible to directly compare all strategies. As such, the analysis conducted direct within-arm comparisons and an indirect between-arm comparison. DFS endpoints and relative DFS benefit were derived from the monotherapy and sequential arms of BIG 1–98. Adverse events were not included as these have not yet been reported. Sensitivity analyses were conducted for the key parameters and assumptions, including the baseline recurrence risk and the duration of carry-over benefit. Costs and utility weights were derived from the literature. The analysis took a Canadian direct payer perspective and drug costs were based on 2008 Canadian average wholesale prices. Costs and outcomes were discounted at 3%. Results: In the monotherapy arms LET had a CE of $16,650 relative to TAM. In the sequential arms LET-TAM had superior QALYGs and cost savings relative to LET and TAM-LET. In economic terms, LET-TAM dominated LET and TAM-LET. In the indirect comparison, LET-TAM dominated LET and TAM-LET and had superior QALYGs at increased cost relative to TAM for a CE of $178. Conclusions: Direct comparisons confirm the economic favourability of LET relative to TAM and establish the dominance of LET-TAM over LET and TAM-LET. These indirect comparisons support the strong economic favourability of LET-TAM relative to TAM in the indirect comparison. In the absence of superior clinical outcomes, economic evaluation is a useful in suggesting a preferred strategy. No significant financial relationships to disclose.
Soluble C5b-9 As a Prognostic Biomarker for Thrombotic Microangiopathy at the Onset of Graft-Versus-Host Disease
Authors: Ang Li, Qian Vicky Wu, Tristan Hilton, Emily Pao, Martin J Schmidt, Noel S Weiss, Stephanie J. Lee, Jingfei Dong, Sangeeta R Hingorani
Journal: Blood (2019)
Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome
Authors: Sanjiv Risal, Yu Pei, Haojiang Lu, Maria Manti, Romina Fornes, Han-Pin Pui, Zhiyi Zhao, Julie Massart, Claes Ohlsson, Eva Lindgren, Nicolas Crisosto, Manuel Maliqueo, Barbara Echiburú, Amanda Ladrón de Guevara, Teresa Sir-Petermann, Henrik Larsson, Mina A. Rosenqvist, Carolyn E. Cesta, Anna Benrick, Qiaolin Deng, Elisabet Stener-Victorin
Journal: Nature Medicine (2019)
Single nucleotide polymorphisms as markers of bacillus Calmette-Guérin intravesical therapy response in non-muscle invasive bladder cancer.
Authors: Shaheen Alanee, Robert James Hamilton, Vijai Joseph, Irina Ostrovnaya, Ilana Rebecca Garcia-Grossman, David J Gallagher, Deepa Pendse, Ashley Marie Regazzi, Jennifer A. Przybylo, Mia Gaudet, Matthew I. Milowsky, Harry W. Herr, Kenneth Offit, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2012)

e15022 Background: A marker of response to Bacillus Calmette-Guérin (BCG) intravesical therapy in high-risk non-muscle invasive bladder cancer (NMIBC) could help avoid unsuccessful BCG treatment and potentially enhance care. This study examines germline single nucleotide polymorphisms (SNPs) as markers of BCG-refractory NMIBC. Methods: Saliva or blood was prospectively collected from patients treated with BCG for NMIBC between 1991 and 2010, treated either at MSKCC or referring centers prior to MSKCC registration. BCG-refractory disease was defined as the presence of pathologically documented tumor in the bladder six months after BCG administration. SNPs were selected based on either reported associations with BCG response or putative mechanisms of BCG activity. Eighty candidate SNPs were genotyped (using the Sequenom Mass ARRAY iPLEX platform) in a discovery set (n=158) and those significantly associated were analyzed in a validation set (n=168). Univariate logistic regression was used to test the association between refractory disease, selected clinical variables, and SNPs. Because center of treatment was found to be a confounding variable (p=0.02), primary analysis was limited to cases treated at a single center (MSKCC), consisting of 276 patients (108 from discovery set and 168 from validation set). Results: Median age of diagnosis of the 276 cases was 65.7 years, 94% diagnosed with high-grade superficial bladder cancer, 35% stage Ta, 30% stage T1, and 35% stage Tis. At six month follow-up, 37 (13.4%) had BCG–refractory disease. Nine SNPs showed significant associations with outcome in the discovery cohort (two SNPs failed genotyping). In primary analysis, One SNP, rs11615, an intronic variant within the ERCC1 gene, was associated with BCG-refractory disease. Patients with CC genotype were 3.6 times more likely to be refractory to BCG compared to TT genotype (OR for each C allele was 1.8: 95% CI 1.1-3; p=0.01). No other factors were found to be predictive. Conclusions: A single nucleotide polymorphism of ERCC1 may be associated with BCG-refractory disease. Validation in independent datasets is needed.
Bile acids associate with glucose metabolism, but do not predict conversion from impaired fasting glucose to diabetes
Authors: Oscar Chávez-Talavera, Matthieu Wargny, Matthieu Pichelin, Amandine Descat, Emmanuelle Vallez, Mostafa Kouach, Edith Bigot-Corbel, Marielle Joliveau, Jean-François Goossens, Cédric Le May, Samy Hadjadj, Rémy Hanf, Anne Tailleux, Bart Staels, Bertrand Cariou
Journal: Metabolism (2019)
Correction to: c-Src confers resistance to mitotic stress through inhibition of DMAP1/Bub3 complex formation in pancreatic cancer
Authors: Jingjie Li, Bin Hu, Ting Wang, Wenhua Huang, Chunmin Ma, Qin Zhao, Lingang Zhuo, Tao Zhang, Yuhui Jiang
Journal: Molecular Cancer (2019)

Following publication of the work [1], authors reported the "flow cytometery plots" panel in Fig. 4e contained an inter-duplication in error.
Durable Remission after Salvage Chemotherapy with Combining Bortezomib and Vorinostat Followed By CD19 CAR-T Therapy in a Patient with MLL-Rearranged ALL after Early Relapse Post Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Nobuhiro Nishio, Kai Wang, Kotaro Narita, Shinsuke Kataoka, Hironobu Kitazawa, Motoharu Hamada, Daisuke Ichikawa, Rieko Taniguchi, Norihiro Murakami, Daiei Kojima, Kyogo Suzuki, Nozomu Kawashima, Eri Nishikawa, Yusuke Okuno, Atsushi Narita, Hideki Muramatsu, Asahito Hama, Shih-Ting Tsao, Maoquan Qin, Huyong Zheng, Lung-Ji Chang, Seiji Kojima, Yoshiyuki Takahashi
Journal: Blood (2017)
Enasidenib Drives Maturation of Human Erythroid Precursors Independently of IDH2
Authors: Ritika Dutta, Tian Y Zhang, Thomas Koehnke, Daniel Thomas, Eric Gars, Melissa Stafford, Yusuke Nakauchi, Satinder Kaur, Raymond Yin, Anupama Narla, Ravindra Majeti
Journal: Blood (2019)
Translational Informatics for Parkinson’s Disease: from Big Biomedical Data to Small Actionable Alterations
Authors: Bairong Shen, Yuxin Lin, Cheng Bi, Shengrong Zhou, Zhongchen Bai, Guangmin Zheng, Jing Zhou
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Parkinson’s disease (PD) is a common neurological disease in elderly people, and its morbidity and mortality are increasing with the advent of global ageing. The traditional paradigm of moving from small data to big data in biomedical research is shifting toward big data-based identification of small actionable alterations. To highlight the use of big data for precision PD medicine, we review PD big data and informatics for the translation of basic PD research to clinical applications. We emphasize some key findings in clinically actionable changes, such as susceptibility genetic variations for PD risk population screening, biomarkers for the diagnosis and stratification of PD patients, risk factors for PD, and lifestyles for the prevention of PD. The challenges associated with the collection, storage, and modelling of diverse big data for PD precision medicine and healthcare are also summarized. Future perspectives on systems modelling and intelligent medicine for PD monitoring, diagnosis, treatment, and healthcare are discussed in the end.
Molecular profiling of non-small cell lung cancer (NSCLC) in Asia with targeted next-generation sequencing (NGS): Interim analysis of a co-operative group study (ATORG-001)
Authors: A.C. Tan, H. Loong, G.F. Ho, A. Seet, B. Chiam, D.Q. Cheah, G.S. Tan, K.H. Lim, J.C.-H. Yang, T.S.K. Mok, D.-W. Kim, D.S.W. Tan
Journal: Annals of Oncology (2019)
Nontuberculosis mycobacteria infections: would there be pharmacodynamics without pharmacokinetics?
Authors: Nakwon Kwak, Margareth Pretti Dalcolmo, Charles L. Daley, Geoffrey Eather, Naoki Hasegawa, Won-Jung Koh, Rachel Thomson, Jakko van Ingen, Jae-Joon Yim
Journal: European Respiratory Journal (2019)

<b>Pharmacokinetic, pharmacodynamic and therapeutic drug monitoring data are useful in optimising treatment for <i>Mycobacteriuam abscessus</i> pulmonary disease, but such data are not routinely collected and analysis for clinical practice is difficult</b>http://bit.ly/2pcTIUn
Acute Lymphoblastic Leukemia with Zinc-Finger Protein 384 (ZNF384)-Related Rearrangements: A Retrospective Analysis from the Ponte Di Legno Childhood ALL Working Group
Authors: Shinsuke Hirabayashi, Ellie Butler, Kentaro Ohki, Nobutaka Kiyokawa, Anke K. Bergmann, Judith M. Boer, Hélène Cavé, Giovanni Cazzaniga, Allen Eng Juh Yeoh, Toshihiko Imamura, Hiroto Inaba, Mignon L. Loh, Ulrika Norén-Nyström, Agata Pastorczak, Lee-Yung Shih, Marketa Zaliova, Oskar A Haas, Christine J. Harrison, Anthony V. Moorman, Atsushi Manabe
Journal: Blood (2019)
Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth
Authors: Meng Cao, Huaijiang Yan, Xuan Han, Ling Weng, Qin Wei, Xiaoyan Sun, Wuguang Lu, Qingyun Wei, Juan Ye, Xueting Cai, Chunping Hu, Xiaoyang Yin, Peng Cao
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. Tumor-associated macrophages (TAMs) display a continuum of different polarization states between tumoricidal M1 phenotype and tumor-supportive M2 phenotypes, with a lower M1/M2 ratio correlating with tumor growth, angiogenesis and invasion. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy. <h3>Methods</h3> A novel EVs-liked ginseng-derived nanoparticles (GDNPs) were isolated and characterized from <i>Panax ginseng</i> C. A. Mey. Using GDNPs as an immunopotentiator for altering M2 polarized macrophages, we analyzed associated surface markers, genes and cytokines of macrophages treated with GDNPs. Mice bearing B16F10 melanoma were treated with GDNPs therapy. Tumor growth were assessed, and TAM populations were evaluated by FACS and IF. <h3>Results</h3> GDNPs significantly promoted the polarization of M2 to M1 phenotype and produce total reactive oxygen species, resulting in increasing apoptosis of mouse melanoma cells. GDNP-induced M1 polarization was found to depend upon Toll-like receptor (TLR)-4 and myeloid differentiation antigen 88 (MyD88)-mediated signaling. Moreover, ceramide lipids and proteins of GDNPs may play an important role in macrophage polarization via TLR4 activation. We found that GDNPs treatment significantly suppressed melanoma growth in tumor-bearing mice with increased presence of M1 macrophages detected in the tumor tissue. <h3>Conclusions</h3> GDNPs can alter M2 polarization both in vitro and in vivo, which contributes to an antitumor response. The polarization of macrophages induced by GDNPs is largely dependent on TLR4 and MyD88 signalling. GDNPs as an immunomodulator participate in mammalian immune response and may represent a new class of nano-drugs in cancer immunotherapy.