tbuckley/cabot-search huggingface dataset:
Enhancement of mitochondrial ROS accumulation and radiotherapeutic efficacy using a Gd-doped titania nanosensitizer
Authors: Yuanyuan Chen, Na Li, Jianbo Wang, Xia Zhang, Wei Pan, Longhai Yu, Bo Tang
Journal: Theranostics (2018)

Radiotherapy is an extensively used treatment modality in the clinic and can kill malignant cells by generating cytotoxic reactive oxygen species (ROS). Unfortunately, excessive dosages of radiation are typically required because only a small proportion of the radiative energy is adsorbed by the soft tissues of a tumor, which results in the nonselective killing of normal cells and severe systemic side effects. An efficient nanosensitizer that makes cancer cells more sensitive to radiotherapy under a relatively low radiation dose would be highly desirable. Methods: In this study, we developed a Gd-doped titania nanosensitizer that targets mitochondria to achieve efficient radiotherapy. Upon X-ray irradiation, the nanosensitizer triggers a "domino effect" of ROS accumulation in mitochondria. This overabundance of ROS leads to mitochondrial permeability transition and ultimately irreversible cell apoptosis. Confocal laser imaging, western blotting and flow cytometry analysis were used to explore the biological process of intrinsic apoptosis induced by the nanosensitizer. Clonogenic survival assay, cell migration and invasion experiments were employed to evaluate the radiosensitizing effect of the nanosensitizer in vitro. Finally, to evaluate the therapeutic outcome of the nanosensitizer in vivo, MCF-7 tumor model was used. Results: Confocal laser images and western blotting data demonstrated that the nanosensitizer in conjunction with X-ray irradiation could induce cell apoptosis in ROS-mediated apoptotic signal pathways. A clonogenic survival assay revealed that cells treated with the prepared nanosensitizer exhibited a lower number of viable cell colonies than that of the nontargeted group under X-ray irradiation. Notably, with only a single dose of radiotherapy, the mitochondria-targeted nanosensitizer elicited the complete ablation of tumors in a mouse model. Conclusion: The designed nanosensitizer in combination with X-ray radiation exposure could be used for radiotherapy against cancer in living cells and in vivo. Moreover, the nanosensitizer with mitochondria targeting played a pivotal role in triggering a "domino effect" of ROS and cell apoptosis. The current strategy could provide new opportunities in designing efficient radiosensitizers for future cancer therapy.
Venous Thromboembolism with Contemporary Lenalidomide-Based Regimens and Adequate Thromboprophylaxis in Newly Diagnosed Multiple Myeloma: A Systemic Review and Meta-Analysis
Authors: Rajshekhar Chakraborty, Saad Ullah Malik, Naimisha Marneni, Alex V. Mejia Garcia, Faiz Anwer, Alok A. Khorana, Navneet S. Majhail
Journal: Blood (2018)
Effects of the Switch to Generic Imatinib in a Cohort of 109 Italian CML Patients - the Gims Study
Authors: Maria Gemelli, Chiara Elena, Margherita Maffioli, Cristina Bucelli, Marianna Rossi, Mattia Bacciocchi, Elena Maria Elli, Maria Grazia Valsecchi, Laura Antolini, Carlo Gambacorti-Passerini
Journal: Blood (2018)
Abstract 12650: Genetic Risk Score and Cardiovascular Mortality in a Portuguese Population
Authors: Isabel M Mendonca, Andreia Pereira, Micaela Neto, Joel Monteiro, Ana C Sousa, Eva Henriques, Ana Freitas, Ilidio Ornelas, Roberto Palma dos Reis
Journal: Circulation (2016)

Several genetic risk scores (GRS) have been associated with cardiovascular disease; however, their role in survival from proven coronary artery disease (CAD) have yield conflicting results. Objective: To evaluate long-term cardiovascular mortality according to the genetic risk score. Methods: A study was performed with a cohort of 1464 CAD patients with angiographic proven CAD who were followed-up prospectively for up to 58.3 (interquartile range 25.8 - 88.1) months. Genotyping of 33 SNP associated with CAD was performed using oligonucleotides probes marked with fluorescence for each allele. GRS was constructed according to the additive model assuming co-dominance and was categorized using the median. Cox Regression analysis was performed to determine independent multivariate predictors of cardiovascular mortality. Kaplan Meier Survival curves compared higher than median GRS vs lower than median GRS and log rank test was calculated. Results: During a mean follow-up of 58.3 months (interquartile range 25.8 - 88.1), 156 patients (10.7%) died, 107 (7.3%) of CV causes. Higher than median GRS (≥26) was associated with reduced cardiovascular survival. Survival analysis with COX regression model adjusted for 5 variables showed that high GRS and diabetes were independent risk factors for cardiovascular mortality (HR=1.58, CI: 1.06 - 2.35, p=0.025; HR=1.80, CI: 1.23-2.63, p=0.003, respectively). At the end of follow-up, the estimated survival probability was 70.8% for high GRS, 80.8% for low GRS (Log rank test 5.6; p=0.018). Conclusions: Besides the classical risk factors control, this work highlights the relevance of the genetic profile in survival from CAD. It is expected that new therapies will be directed to gene targets with proven value in cardiovascular survival.
One-Session Treatment of Specific Phobias in Children: Recent Developments and a Systematic Review
Authors: Thompson E. Davis, Thomas H. Ollendick, Lars-Göran Öst
Journal: Annual Review of Clinical Psychology (2018)

One-Session Treatment is a well-established evidence-based treatment for specific phobias in youths that incorporates reinforcement, cognitive challenges, participant modeling, psychoeducation, and skills training into a single, massed session of graduated exposure. This review begins by briefly examining the phenomenology, etiology, epidemiology, and assessment of specific phobias and then pivots to a description of One-Session Treatment. We examine the use of One-Session Treatment with children and adolescents, briefly discussing its components and application, and subsequently review almost two decades of research supporting its efficacy. Finally, we propose future directions for research and practice.
Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum
Authors: WonJae Lee, Song Yi Ko, Muhaned S. Mohamed, Hilary A. Kenny, Ernst Lengyel, Honami Naora
Journal: The Journal of Experimental Medicine (2018)

Ovarian cancer preferentially metastasizes to the omentum, a fatty tissue characterized by immune structures called milky spots, but the cellular dynamics that direct this tropism are unknown. Here, we identified that neutrophil influx into the omentum is a prerequisite premetastatic step in orthotopic ovarian cancer models. Ovarian tumor–derived inflammatory factors stimulated neutrophils to mobilize and extrude chromatin webs called neutrophil extracellular traps (NETs). NETs were detected in the omentum of ovarian tumor–bearing mice before metastasis and of women with early-stage ovarian cancer. NETs, in turn, bound ovarian cancer cells and promoted metastasis. Omental metastasis was decreased in mice with neutrophil-specific deficiency of peptidylarginine deiminase 4 (PAD4), an enzyme that is essential for NET formation. Blockade of NET formation using a PAD4 pharmacologic inhibitor also decreased omental colonization. Our findings implicate NET formation in rendering the premetastatic omental niche conducive for implantation of ovarian cancer cells and raise the possibility that blockade of NET formation prevents omental metastasis.
Letter by Ge et al Regarding Article, “Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study”
Authors: Hong-Wei Ge, Zeng Wang, Fei-Juan Kong
Journal: Circulation (2018)

We congratulate Roberts et al 1 for their refined work recently published in Circulation.The authors performed a multicenter prospective cohort study to determine the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome in patients after cardiac arrest.The findings of this randomized trial indicate that early hyperoxia exposure after resuscitation from cardiac arrest is independently associated with death and poor neurological function at hospital discharge.The neurological evaluation used in the present study was based on a modified Rankin scale, which is a simple test devised for assessing patients' independent daily living and is inadequate for assessing cognitive prognosis, when mild cognitive dysfunction is a real concern in the surviving patients after cardiac arrest. 2,3Thus, it seems reasonable to deduce that the findings of the present study may not lead to changes in practice before patients' recovery of cognitive function are investigated by means of recent advancements in neurological assessment.Moreover, using intravenous propofol anesthesia appears to increase mortality after cardiac surgery in comparison with halogenated agents. 4A preclinical study has shown that propofol may lead to the impairment of brain metabolism during hypothermic circulatory arrest, 5 which may result in the exacerbated neurological disability of the survivors of cardiac arrest who received early hyperoxia exposure in the current trial. 4Therefore, we wonder whether the dose and timing of propofol in the intensive care unit affect patient outcomes.We would appreciate if the authors could provide additional information on this issue.
New validated diagnostic criteria for pyoderma gangrenosum
Authors: Emanual Maverakis, Stephanie T. Le, Jeffrey Callen, Uwe Wollina, Angelo Valerio Marzano, Daniel Wallach, Courtney Schadt, Yocasta C. Martinez-Alvarado, Michelle Y. Cheng, Chelsea Ma, Alexander Merleev, Anthony Ormerod, Fiona Craig, Finja Jockenhofer, Joachim Dissemond, Katrin Salva, Hywel C. Williams, David Fiorentino
Journal: Journal of the American Academy of Dermatology (2018)
Abstract MP32: Muscular Strength and Type 2 Diabetes Prevention
Authors: Duck-chul Lee, Angelique Brellenthin, Xuemei Sui, Steven Blair
Journal: Circulation (2018)

Introduction: There is little evidence on the effects of muscular strength, independent of cardiorespiratory fitness, on the development of type 2 diabetes. Hypothesis: We hypothesised that muscular strength, independent of cardiorespiratory fitness, has significant benefits in type 2 diabetes prevention. Methods: Participants were 5,578 men and women aged 18 to 100 years (mean age, 44) who received preventive medical examinations during 1980-2006 in the Aerobics Center Longitudinal Study. Participants were free of myocardial infarction, stroke, cancer, and diabetes at baseline. Total body muscular strength was quantified by combining 1 repetition maximum (1-RM) measures for leg and bench presses and categorized into three groups, lower (weak), middle, and upper (strong), based on the tertiles (thirds) of muscular strength. Cardiorespiratory fitness was measured by a maximal treadmill exercise test. Type 2 diabetes was defined as a fasting plasma glucose level of ≥126 mg/dl, a history of diabetes, or current insulin therapy. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident type 2 diabetes by muscular strength after adjusting for baseline age, sex, examination year, body mass index (BMI), current smoking, heavy alcohol drinking, parental history of diabetes, hypertension, hypercholesterolemia, glucose level, and maximum treadmill test time. Results: During an average follow-up of 8 years, 270 (4.8%) individuals developed type 2 diabetes. Compared with the individuals in the lower third of muscular strength, individuals in the middle third had a 30% lower risk of developing type 2 diabetes (HR: 0.70, 95% CI: 0.51-0.95), whereas no significant benefit was found in individuals in the upper third (HR: 1.16, 95% CI: 0.86-1.57) after adjusting for potential confounders and cardiorespiratory fitness. We found similar results in men and women, young (&lt;50 years) and old (≥50 years), and normal (BMI &lt;25 kg/m 2 ) and overweight/obese (BMI ≥25 kg/m 2 ) individuals. In the combined analysis of muscular strength and cardiorespiratory fitness, we also found similar results that individuals in the middle third of muscular strength showed lower risks of developing type 2 diabetes in both low (lower 50%) and high (upper 50%) cardiorespiratory fitness, compared with individuals in the lower third of muscular strength and low cardiorespiratory fitness. Conclusions: We found that a moderate level of muscular strength, independent of cardiorespiratory fitness, is associated with a lower risk of developing type 2 diabetes. Additional studies on the dose-response relationship of muscular strength and incident type 2 diabetes are warranted.
An integrative approach for building personalized gene regulatory networks for precision medicine
Authors: Monique G. P. van der Wijst, Dylan H. de Vries, Harm Brugge, Harm-Jan Westra, Lude Franke
Journal: Genome Medicine (2018)

Only a small fraction of patients respond to the drug prescribed to treat their disease, which means that most are at risk of unnecessary exposure to side effects through ineffective drugs. This inter-individual variation in drug response is driven by differences in gene interactions caused by each patient's genetic background, environmental exposures, and the proportions of specific cell types involved in disease. These gene interactions can now be captured by building gene regulatory networks, by taking advantage of RNA velocity (the time derivative of the gene expression state), the ability to study hundreds of thousands of cells simultaneously, and the falling price of single-cell sequencing. Here, we propose an integrative approach that leverages these recent advances in single-cell data with the sensitivity of bulk data to enable the reconstruction of personalized, cell-type- and context-specific gene regulatory networks. We expect this approach will allow the prioritization of key driver genes for specific diseases and will provide knowledge that opens new avenues towards improved personalized healthcare.
Sustained Disease Control for Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: An Updated Analysis of Juliet, a Global Pivotal Phase 2 Trial of Tisagenlecleucel
Authors: Stephen J. Schuster, Michael R. Bishop, Constantine Tam, Peter Borchmann, Ulrich Jaeger, Edmund K. Waller, Harald Holte, Joseph P. McGuirk, Samantha Jaglowski, Kensei Tobinai, Charalambos Andreadis, Isabelle Fleury, Stephan Mielke, Takanori Teshima, Jason R. Westin, Veronika Bachanova, Stephen Ronan Foley, P Joy Ho, John M. Magenau, Nina D. Wagner-Johnston, Koji Kato, Marie Jose Kersten, Koen Van Besien, Jufen Chu, Aline Jary, Özlem Anak, Gilles Salles, Richard Thomas T. Maziarz
Journal: Blood (2018)
Controversies About Lyme Disease
Authors: Scott Santarella, Timothy J. Sellati
Journal: JAMA (2018)

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 13048: The Impact of Statin-Ezetimibe Combination Therapy in Patients With Decreased Cholesterol Absorption Ability
Authors: Kenshi Yamanaga, Kenichi Tsujita, Seigo Sugiyama, Hitoshi Sumida, Hideki Shimomura, Takuro Yamashita, Naohiro Komura, Kenji Sakamoto, Hideki Oka, Koichi Nakao, Sunao Nakamura, Masaharu Ishihara, Kunihiko Matsui, Naritsugu Skaino, Natsuki Nakamura, Nobuyasu Yamamoto, Shunichi Koide, Toshiyuki Matsumura, Kazuteru Fujimoto, Ryusuke Tsunoda, Yasuhiro Morikami, Koushi Matsuyama, Shuichi Oshima, Koichi Kaikita, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2015)

Introduction: Ezetimibe (EZE) is a cholesterol absorption inhibitor and its clinical benefit, as combined with statin for pts with coronary artery disease (CAD), was shown by IMPROVE-IT trial. Campesterol (camp) is the cholesterol absorption marker and the benefit of EZE/statin combination therapy for pts with low camp (LC) value, in whom EZE appears to ineffective, is not clearly understood. The PRECISE-IVUS (Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound) trial was a prospective, randomized, controlled, multicenter study evaluating the effects of EZE addition to atorvastatin (atorva), compared with atorva monotherapy, on coronary atherosclerosis evaluated by IVUS and lipid profile. Hypothesis: In this study, we investigated the effect of EZE for pts with the LC value. Methods: 246 pts undergoing IVUS-guided percutaneous coronary intervention were randomized to EZE/atorva combination (EA) group or atorva alone (A) group. The dosage of atorva was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol (LDL-C) below 70mg/dL. Serial volumetric IVUS was performed at baseline and 9–12 months follow-up to quantify the coronary plaque response in 202 patients. Results: There were significantly positive correlation between baseline LDL-C level and baseline camp value (R=0.399, p&lt;0.01), but no significant difference between baseline camp value and the presence of prior statin use. Baseline LDL-C level was significantly lower in LC groups (LC group vs. high camp group; 100.2±25.5mg/dL vs. 116.8±23.5mg/dL, respectively, p&lt;0.0001). In the LC group, the delta LDL-C ratio (follow up LDL-C - baseline LDL-C / baseline LDL-C) was significantly lower in EA group compared with A group (-37.2±16.2% vs. -23.4±25.1%, p=0,009) and EA group showed significantly greater reduction in delta percent atheroma volume, compared with A group (-2.2 [-4.1 to -0.1]% vs. -0.3 [-1.6 to 1.1]%, p=0.04). Conclusions: Even in pts with CAD and LC value, statin-EZE combined therapy showed significantly decreased LDL-C and regressed coronary plaque burden. Even if the cholesterol absorption ability is declined, EZE-statin combined therapy might be the promising option for pts with CAD.
A lexicon for gender bias in academia and medicine
Authors: Esther K Choo, Robert F DeMayo, None Glaucomflecken
Journal: BMJ (2018)

Mansplaining is the tip of the iceberg Many of the experiences of women in the workforce are so patterned and commonplace they have spawned an emerging vocabulary, which includes terms like mansplaining (explaining something in a condescending or patronising way, typically to a woman),1 bropropriation (when a man takes credit for a woman's idea),2 manel (a panel of speakers populated entirely by men),3 and himpathy (the "inappropriate and disproportionate sympathy powerful men often enjoy in cases of sexual assault, intimate partner violence, homicide, and other misogynistic behavior").4 Here, we propose a number of additions to the vernacular, which are likely to remain relevant for the foreseeable future.5
Inappropriate Grading of Adverse Events in Cancer Clinical Trials
Authors: Sheng Zhang, Hongxi Xue
Journal: JAMA Oncology (2018)

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