tbuckley/cabot-search huggingface dataset:
Overestimating the Benefit of Cancer Drugs
Authors: Vinay Prasad
Journal: JAMA Oncology (2017)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
The distinct biological implications of Asxl1 mutation and its roles in leukemogenesis revealed by a knock-in mouse model
Authors: Yueh-Chwen Hsu, Yu-Chiao Chiu, Chien-Chin Lin, Yuan-Yeh Kuo, Hsin-An Hou, Yi-Shiuan Tzeng, Chein-Jun Kao, Po-Han Chuang, Mei-Hsuan Tseng, Tzu-Hung Hsiao, Wen-Chien Chou, Hwei-Fang Tien
Journal: Journal of Hematology & Oncology (2017)

Additional sex combs-like 1 (ASXL1) is frequently mutated in myeloid malignancies. Recent studies showed that hematopoietic-specific deletion of Asxl1 or overexpression of mutant ASXL1 resulted in myelodysplasia-like disease in mice. However, actual effects of a "physiological" dose of mutant ASXL1 remain unexplored. We established a knock-in mouse model bearing the most frequent Asxl1 mutation and studied its pathophysiological effects on mouse hematopoietic system. Heterozygotes (Asxl1 tm/+ ) marrow cells had higher in vitro proliferation capacities as shown by more colonies in cobblestone-area forming assays and by serial re-plating assays. On the other hand, donor hematopoietic cells from Asxl1 tm/+ mice declined faster in recipients during transplantation assays, suggesting compromised long-term in vivo repopulation abilities. There were no obvious blood diseases in mutant mice throughout their life-span, indicating Asxl1 mutation alone was not sufficient for leukemogenesis. However, this mutation facilitated engraftment of bone marrow cell overexpressing MN1. Analyses of global gene expression profiles of ASXL1-mutated versus wild-type human leukemia cells as well as heterozygote versus wild-type mouse marrow precursor cells, with or without MN1 overexpression, highlighted the association of in vivo Asxl1 mutation to the expression of hypoxia, multipotent progenitors, hematopoietic stem cells, KRAS, and MEK gene sets. ChIP-Seq analysis revealed global patterns of Asxl1 mutation-modulated H3K27 tri-methylation in hematopoietic precursors. We proposed the first Asxl1 mutation knock-in mouse model and showed mutated Asxl1 lowered the threshold of MN1-driven engraftment and exhibited distinct biological functions on physiological and malignant hematopoiesis, although it was insufficient to lead to blood malignancies.
Immune response and adverse events to influenza vaccine in cancer patients undergoing PD-1 blockade.
Authors: Heinz Philipp Laubli, Cathrin Balmelli, Lukas Kaufmann, Michal Stanczak, Mohammedyaseen Syedbasha, Dominik Vogt, Beat Mueller, Oliver Gautschi, Frank Stenner, Alfred Zippelius, Adrian Egli, Sacha Rothschild
Journal: Journal of Clinical Oncology (2017)

e14523 Background: Cancer patients (pts) are at risk to develop complications when infected with seasonal influenza viruses. Current guidelines propose that pts on PD-1 directed therapies may receive concurrent inactivated influenza immunization if not medically contraindicated. In this observational study, we aimed to assess the vaccine induced immune response and safety of immunotherapy and influenza vaccine. Methods: Metastatic cancer pts treated with at least one dose of either nivolumab or pembrolizumab were vaccinated with a trivalent inactive influenza vaccination between October and November 2015. Partners of the pts were vaccinated and included in our analysis as age-matched controls. Antibody titers against vaccine virus strains were measured by hemagglutination inhibition assay at days 7, 30, 60 and 180. Cytokine/chemokine profile and changes in peripheral immune cells were assessed in cancer pts at the same time points. Immune-related adverse events (irAE) were documented according to CTCAE v4.0. Results: We included 23 pts and 7 age-matched healthy controls. Median time between initiation of PD-1 inhibition and influenza vaccination was 74 days (range, 44-57). 22 pts were treated with nivolumab and 1 pt with pembrolizumab. 16 pts had a diagnosis of non-small cell lung cancer, 3 pts had renal cell carcinoma and 3 pts a malignant melanoma. In total, 12 pts (52.2%) experienced an irAE. 6 pts (26.1%) had grade 3 or 4 (G3/4) irAEs. This frequency seems to be higher than reported in the literature. G3/4 irAEs include colitis (n = 2), encephalitis (n = 1), vasculitis (n = 1), pneumonitis (n = 1), peripheral neuritis (n = 1). There was no major difference over time in the generation of antibody titers against strains in the vaccine. Peripheral leukocyte counts and cytokine/inflammatory chemokine levels were unchanged after vaccination. We did not observe unexpected local toxicities at the injection site. Conclusions: The seasonal influence vaccination reaches a protective range in these pts. Unexpectedly, however, an increased rate of clinically relevant irAEs was observed. Confirmation in a larger population and mechanistic understanding is required.
Rationale and design of the AdaptResponse trial: a prospective randomized study of cardiac resynchronization therapy with preferential adaptive left ventricular‐only pacing
Authors: Gerasimos Filippatos, David Birnie, Michael R. Gold, Bart Gerritse, Ahmad Hersi, Sandra Jacobs, Kengo Kusano, Christophe Leclercq, Wilfried Mullens, Bruce L. Wilkoff
Journal: European Journal of Heart Failure (2017)

Abstract The AdaptResponse trial is designed to test the hypothesis that preferential adaptive left ventricular‐only pacing with the AdaptivCRT ® algorithm reduces the incidence of the combined endpoint of all‐cause mortality and intervention for heart failure (HF) decompensation, compared with conventional cardiac resynchronization therapy (CRT), among patients with a CRT indication, left bundle branch block (LBBB) and normal atrioventricular (AV) conduction. The AdaptResponse study is a prospective, randomized, controlled, single‐blinded, multicentre, clinical trial ( ClinicalTrials.gov Identifier: NCT02205359), conducted at up to 200 centres worldwide. Following enrolment and baseline assessment, eligible subjects will be implanted with a CRT system containing the AdaptivCRT algorithm, and randomized in a 1:1 fashion to either a treatment (‘AdaptivCRT’) or control (‘Conventional CRT’) group. The study is designed to observe a primary endpoint in 1100 patients (‘event‐driven’) and approximately 3000 patients will be randomized. The primary endpoint is the composite of all‐cause mortality and intervention for HF decompensation; secondary endpoints include all‐cause mortality, intervention for HF decompensation, clinical composite score (CCS) at 6 months, atrial fibrillation, quality of life measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), health outcome measured by the EQ‐5D instrument, all‐cause readmission after a HF admission, and cost‐effectiveness. The AdaptResponse clinical trial is powered to assess clinical endpoints and is expected to provide definitive evidence on the incremental utility of AdaptivCRT‐enhanced CRT systems.
Stories Doctors Tell
Authors: Tracy Moniz, Lorelei Lingard, Chris Watling
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Abstract 17277: Myocardial Rescue by Mesenchymal Stem Cell via Tunneling Nanotube Formation
Authors: Huaxiao Yang, Raymond B Runyan, Tom K Borg, Roger Markwald, Meifeng Xu, Bruce Z Gao
Journal: Circulation (2014)

Objectives: Mesenchymal stem cell (MSC) shows promising therapeutic potentials for heart diseases in numerous animal studies and clinical trials. The cardiogenic transdifferentiation and paracrine factors delivery of MSCs are generally accepted mechanisms for myocardial rescue. Recent studies suggest that the rescue may also be achieved by direct delivery of subcellular organelles such as mitochondria. Tunneling nanotube (TNT) formation between MSCs and various damaged cell types has been observed both in vitro and in vivo for assisting organelle transfer. Based on our recent observation in a cell patterning-based in vitro assay, it is found that mitochondria are transferred from MSCs to neonatal cardiomyocytes (NCMs) through TNTs to enhance myocyte survival. Adequate investigation of hetero-paired TNTs is hampered by their random formation in standard cell culture and the difficulty of capturing them in vivo. Accordingly, a PDMS (polydimethylsiloxane) biochip-based coculture model was microfabricated to enable more consistent examination of TNT formation and mitochondrial transfer. Methods: Rat MSC (GFP tagged in green) and 3-day NCMs (w or w/0 treatment of 1 μg/ml lipopolysaccharide (LPS)) were introduced into a two-channel microfluidics-based biochip (Figure 1A) microfabricated with PDMS, and TNTs were guided to form in microchannels between the two cell types. The numbers of TNT formed between MSC and LPS treated or untreated NCM were counted per biochip after 24 hours coculturing. Then the sample was stained with annexin V to evaluate the cardiac stress of NCMs. Results and Discussion: It was observed that mitochondria were transferred unidirectionally from MSCs to NCMs via TNT (Figure 1B), irrespective of the TNT’s direction of formation. NCMs in stressed conditions triggered more TNT formation in red of annexin V staining with MSCs than the control (Figure 1C). It suggests that a rescue effect may be produced by TNT-mediated mitochondrial transfer.
Sensitivity Analysis in Observational Research: Introducing the E-Value
Authors: Tyler J. VanderWeele, Peng Ding
Journal: Annals of Internal Medicine (2017)

Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment–outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.
Accelerated Evolution and Functional Divergence of the Dim Light Visual Pigment Accompanies Cichlid Colonization of Central America
Authors: Frances E. Hauser, Katriina L. Ilves, Ryan K. Schott, Gianni M. Castiglione, Hernán López-Fernández, Belinda S.W. Chang
Journal: Molecular Biology and Evolution (2017)

Cichlids encompass one of the most diverse groups of fishes in South and Central America, and show extensive variation in life history, morphology, and colouration. While studies of visual system evolution in cichlids have focussed largely on the African rift lake species flocks, Neotropical cichlids offer a unique opportunity to investigate visual system evolution at broader temporal and geographic scales. South American cichlid colonization of Central America has likely promoted accelerated rates of morphological evolution in Central American lineages as they encountered reduced competition, renewed ecological opportunity, and novel aquatic habitats. To investigate whether such transitions have influenced molecular evolution of vision in Central American cichlids, we sequenced the dim-light rhodopsin gene in 101 Neotropical cichlid species, spanning the diversity of the clade. We find strong evidence for increased rates of evolution in Central American cichlid rhodopsin relative to South American lineages, and identify several sites under positive selection in rhodopsin that likely contribute to adaptation to different photic environments. We expressed a Neotropical cichlid rhodopsin protein invitro for the first time, and found that while its spectral tuning properties were characteristic of typical vertebrate rhodopsin pigments, the rate of decay of its active signalling form was much slower, consistent with dim light adaptation in other vertebrate rhodopsins. Using site-directed mutagenesis combined with spectroscopic assays, we found that a key amino acid substitution present in some Central American cichlids accelerates the rate of decay of active rhodopsin, which may mediate adaptation to clear water habitats.
Cancer cell targeting and therapy by growth hormone-nano-diamond complex
Authors: Chia-Ching Chang, Pei-Hsin Chen, Hsuen-Liang Chu, Jen-Yin Su, Jui-I Chao, Chia-Liang Cheng, Jyh Shin Chen
Journal: Clinical Cancer Research (2007)

A48   In this study, we have developed a novel strategy to destroy the growth hormone receptor containing membrane of cancer cells, A549 lung carcinoma cells. The cell was targeted with recombinant growth hormone-nanodiamond (rGHND) complex, and rGHND could be triggered explosion with high intensity pulse laser, only. Meanwhile, we found that there is no cytotoxicity of rGHND and the complex can be recognized by the growth hormone receptors (GHR) of A549 cells. Interestingly, the cells, CHO-K1, without GHR were not destroyed by exposing with the high energy of pulse laser. In contrast, the number of A549 depleted around 60%, twenty four hours after the laser treatment. Both atomic force microscope and electron microscope images indicated that the ND expanded from 5 nm to 95 nm after laser irradiation. These nano-scale explosions destroyed cancer cell membrane and made them apoptosis. Accordingly, we designate this technique as nano-surgery, which may contribute to the non-conventional therapeutic strategies in the cancer therapy or other intermolecular inhibition.
Psychological impact of electrocardiogram screening in National Collegiate Athletic Association athletes
Authors: Irfan M Asif, Scott Annett, Joseph A Ewing, Ramy Abdelfattah, Brittan Sutphin, Kyle Conley, Justin Rothmier, Kimberly G Harmon, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2017)

Purpose Determine the psychological impact of false-positive ECG screening in National Collegiate Athletic Association (NCAA) athletes. Methods Athletes representing seven NCAA institutions received a standardised history, physical examination and ECG interpreted using the 2013 Seattle Criteria. Assessments of health attitudes, anxiety and impact of screening on sport were conducted using validated prescreen and postscreen measurements. Results 1192 student-athletes participated (55.4% male, median age 19 years, 80.4% Caucasian). 96.8% of athletes had a normal cardiovascular screen, 2.9% had a false-positive ECG and 0.3% were diagnosed with a serious cardiac condition. Prior to screening, 4.5% worried about potentially harbouring cardiac disease and 70.1% preferred knowing about an underlying condition, rather than play sports without this knowledge. There was no difference in anxiety described by athletes with a normal versus false-positive screen (p=0.369). Reported anxiety levels during screening also did not differ when analysed by different gender, race, division of play or sport. Athletes with normal and false-positive screens had similar levels of satisfaction (p=0.714) and would recommend ECG screening to other athletes at similar rates (p=0.322). Compared with athletes with a normal screen, athletes with false-positive results also reported feeling safer during competition (p&gt;0.01). In contrast, athletes with false-positive screens were more concerned about the possibility of sports disqualification (p&lt;0.001) and the potential for developing a future cardiac condition (p&lt;0.001). Conclusions Athletes with a false-positive ECG do not experience more anxiety than athletes with a normal screen but do express increased concern regarding sports disqualification and the development of a cardiac disorder. These findings do not justify avoiding advanced cardiovascular screening protocols. Further understanding of athlete experiences could better prepare the practising physician to counsel athletes with an abnormal ECG.
PHISIOLOGIC VARIABLES AND PHARMCOKINETICS IMIPENEM DURING ENLP. A SINGLE CENTER TRANSPLANTATION EXPERIENCE
Authors: Fanelli, A Costamagna, P Persico, G Rotondo, L Mascia, S Corcione, L Baietto, A D'Avolio, Pp Terragni, Fg De Rosa, R Bonato, L Del Sorbo, R Boffini, M Rinaldi, Vm Ranieri
Journal: Intensive Care Medicine (2014)
P<scp>OEMS</scp>syndrome: 2017 Update on diagnosis, risk stratification, and management
Authors: Angela Dispenzieri
Journal: American Journal of Hematology (2017)

Abstract Disease Overview POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis The diagnosis of POEMS syndrome is made with 3 of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. Risk Stratification Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy Risk‐Adapted Therapy For those patients with a dominant sclerotic plasmacytoma, first‐line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3–6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low‐dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. The benefit of anti‐VEGF antibodies is conflicting. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.
EFFECTS OF A PREVENTION PROGRAM FOCUSED ON HIP JOINT FUNCTION ON THE INCIDENCE OF ANTERIOR CRUCIATE LIGAMENT INJURIES IN FEMALE BASKETBALL PLAYERS
Authors: Yorikatsu Ohmi, Norikazu Hirose
Journal: British Journal of Sports Medicine (2017)

Background Previous meta-analyses have revealed that effective programs to prevent anterior cruciate ligament (ACL) injuries in female basketball players have not been established. Objective To investigate the effects of an ACL injury prevention program focused on improving hip joint function in female basketball players. Design Cohort study. Setting Intervention study for well-trained varsity athletes. Patients (or Participants) Four hundred eighty-nine (180 intervention and 309 control) female varsity division II basketball players (18–22 years of age) participated in this study. Interventions (or Assessment of Risk Factors) The prevention program consisted of education (injury mechanism, neutral position, etc.) and neuromuscular training to improve hip joint function (jump-landing exercise with a band, hip external rotator and abductor strength training, and balance exercises). Players were guided through this program by several physical therapists. They were instructed to keep the knee and toe in a neutral position in the jump-landing exercise. The intervention group performed this program three times a week throughout the season. The control group maintained their routine warm-up session. All ACL injuries were verified by arthroscopy or magnetic resonance imaging findings. Main Outcome Measurements The 1000 athlete-exposure (1000 AE) and relative risk index (intervention vs. control) of ACL injuries were calculated and compared between the groups using the χ 2 test. Statistical significance was set at P&lt;0.05. Results Three ACL injuries occurred in the intervention group, whereas 16 occurred in the control group. The incidence of injury in the intervention and control groups was 0.08/1000 AE and 0.25/1000 AE, respectively. The relative risk index was 0.32 (95% CI, 0.092–1.086; P=0.053, χ 2 test). Conclusions Prevention programs to reduce ACL injuries may be beneficial in well-trained female basketball players.