tbuckley/cabot-search huggingface dataset:
How Much of an Advance Is the Addition of Samidorphan to Olanzapine?
Authors: Robert W. Buchanan
Journal: American Journal of Psychiatry (2020)

Antipsychotic medications remain the mainstay of the pharmacological treatment of people with schizophrenia.They are relatively effective for the treatment of the positive symptoms of the illness and the prevention of relapse and rehospitalization, but have limited treatment benefits for the two illness components that are most associated with functional impairments: negative symptoms and cognitive impairments (1-4).Almost all antipsychotic medications work through dopamine D 2 receptor antagonism and exhibit roughly equivalent efficacy (5).The one notable exception is clozapine, which is the only antipsychotic medication that has been approved for people with treatment-resistant schizophrenia (1).There is also some evidence to suggest that olanzapine may be more effective than other firstand second-generation antipsychotic medications (6).However, olanzapine is associated with significant weight gain and the development of various metabolic abnormalities, which limits the use of this potentially more effective agent.The development of an effective strategy to minimize olanzapineinduced weight gain and metabolic abnormalities would have the potential benefit of allowing for increased use of this agent.The study by Correll and colleagues (7) in this issue of the Journal addresses a novel approach to reducing olanzapineinduced weight gain.Samidorphan is a m-opioid receptor antagonist and a partial agonist at the ĸandd-opioid receptors (8).The m-, ĸ-, and d-opioid receptors have been implicated in the regulation of weight gain and metabolism (9-11).In order to test the hypothesis that the addition of samidorphan to olanzapine would significantly reduce or prevent olanzapine-associated weight gain, the authors conducted a 24-week, double-blind, placebo-controlled randomized clinical trial in people with schizophrenia, which compared olanzapine (10-20 mg) plus a fixed dose of samidorphan (10 mg) to olanzapine plus placebo.The co-primary outcome measures were percent change from baseline in weight and the percentage of people who gained more than 10% of their baseline body weight.The key secondary endpoint was the percentage of people who gained more than 7% of their baseline weight.Other outcome measures included waist circumference and various metabolic indices.The authors found that combined olanzapine/samidorphan compared with olanzapine/placebo resulted in significantly less weight gain, fewer participants who gained .10% or .7% of their baseline weight, and a smaller increase in waist
Therapeutically Targetable Activating c-ABL1 Mutations in Philadelphia Chromosome-Negative Leukemias
Authors: Samantha L Savage, Julia E. Maxson, Christopher A. Eide, Chelsea Jenkins, Melissa L Abel, Anna M. Reister Schultz, Daniel Bottomly, Beth Wilmot, Shannon Mcweeney, Cristina E. Tognon, Jeffrey W. Tyner, Brian J. Druker
Journal: Blood (2017)
The disease burden of peanut allergy in Denmark measured by disability‐adjusted life years (DALYs)
Authors: Lea S. Jakobsen, Kirsten Pilegaard, Sara M. Pires, Katrine L. Bøgh
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
411P Impact of pre-treatment AXL expression on osimertinib efficacy in patients with non-small cell lung cancer with EGFR mutation
Authors: Y. Taniguchi, T. Yamada, A. Yoshimura, H. Taniguchi, K. Kaira, S. Atagi, S. Yano, K. Takayama
Journal: Annals of Oncology (2020)
260P A phase I study of copanlisib, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor, in Chinese patients with relapsed indolent non-Hodgkin lymphoma (iNHL)
Authors: Y. Song, W. Liu, Y. Niu, G. Cisternas, F. Huang, J. Garcia-Vargas, B.H. Childs, A. Mehra, T. Li, F. Hiemeyer, J. Zhai, S. Reschke, C. Granvil, J. Zhu
Journal: Annals of Oncology (2020)
Mortality and major disease risk among migrants of the 1991–2001 Balkan wars to Sweden: A register-based cohort study
Authors: Edda Bjork Thordardottir, Li Yin, Arna Hauksdottir, Ellenor Mittendorfer-Rutz, Anna-Clara Hollander, Christina M. Hultman, Paul Lichtenstein, Weimin Ye, Filip K. Arnberg, Fang Fang, Emily A. Holmes, Unnur Anna Valdimarsdottir
Journal: PLoS Medicine (2020)

In recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991-2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.We conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991-2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34-1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29-1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08-1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15-1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14-1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96-10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48-0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51-0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.Our findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.
Cellular expression and localization of DNA exonucleases, Trex, and their response to chemotherapeutic compounds in different tumor cell lines
Authors: Chuan-Jen C. J. Wang, Guangwei Yang, Hua-Mei Chang, Wing Lam, Chih-Hung Hsu, Yung-Chi Cheng
Journal: Cancer Research (2005)

1782  Trex1 and Trex2 are two human proteins bearing 3’ to 5’ exonuclease activities with unclear function. In this study, we demonstrated that the amount of Trex1 protein expression was different in different cell lines. Among those cell lines examined, Trex1 was expressed in KB, HeLa, C666 and all the lymphoid tumor cell lines we studied, but undetectable in HepG2 and RKO cells. Poor expression, if any, of Trex1 mRNA in both HepG2 and RKO cells explained why Trex1 proteins were undetectable in them. The levels of Trex1 mRNA expression in different cell lines are in the order: H9 > CEM > KB = HeLa > HepG2 > RKO. In all cell lines we studied, however, no Trex2 protein could be detected with the same size as the recombinant protein. The localization of Trex1 was studied among the Trex1-expressing cells in which Trex1 appeared in both the cytoplasm and nucleus in KB cells, whereas in H9 cells, it appeared primarily in the cytoplasm. The DNA damaging agents including camptothecin, etoposide, cisplatin, and cytotoxic L-nucleoside analog, such as L-OddC, could cause Trex1 protein induction in concentration-dependent manners, and the levels of Trex1 mRNA were also increased accordingly, suggesting that Trex1 protein is probably involved in DNA repair mechanisms and that its induction was through up-regulation of the Trex1 mRNA expression. Cytotoxic D-deoxynucleoside analog gemcitabine and non-cytotoxic antiviral L-nucleoside analog 3TC, however, could not cause the same effects. Upon CPT treatment, Trex1 exonuclease activity was correspondingly increased with the induced Trex1 proteins; different cell types, such as KB and H9 cells, responded similarly to cause Trex1 induction. Nevertheless, nuclear translocation of Trex1 was more apparent in KB cells than in H9 cells. In summary, the expression and localization of Trex1 is cell-type dependent and some but not all of the chemotherapeutic agents can induce its expression. (This work is supported by grant RO1 AI38204 and RO1 CA63477 from NIH, USA) Dr. Y.C. Cheng is a fellow of National Foundation for Cancer Research.
Patient‐Derived Prostate Cancer Explants: A Clinically Relevant Model to Assess siRNA‐Based Nanomedicines
Authors: Terence Tieu, Swati Irani, Kayla L. Bremert, Natalie K. Ryan, Marcin Wojnilowicz, Madison Helm, Helmut Thissen, Nicolas H. Voelcker, Lisa M. Butler, Anna Cifuentes‐Rius
Journal: Advanced Healthcare Materials (2020)

Abstract Over the last thirty years, research in nanomedicine has widely been focused on applications in cancer therapeutics. However, despite the plethora of reported nanoscale drug delivery systems that can successfully eradicate solid tumor xenografts in vivo, many of these formulations have not yet achieved clinical translation. This issue particularly pertains to the delivery of small interfering RNA (siRNA), a highly attractive tool for selective gene targeting. One of the likely reasons behind the lack of translation is that current in vivo models fail to recapitulate critical elements of clinical solid tumors that may influence drug response, such as cellular heterogeneity in the tumor microenvironment. This study incorporates a more clinically relevant model for assessing siRNA delivery systems; ex vivo culture of prostate cancer harvested from patients who have undergone radical prostatectomy, denoted patient‐derived explants (PDE). The model retains native human tissue architecture, microenvironment, and cell signaling pathways. Porous silicon nanoparticles (pSiNPs) behavior in this model is investigated and compared with commonly used 3D cancer cell spheroids for their efficacy in the delivery of siRNA directed against the androgen receptor (AR), a key driver of prostate cancer.
Abstract 12159: Thromboembolic Risk in Patients With Peri-Device Leak After Watchman Implantation
Authors: Chintan Trivedi, Sanghamitra Mohanty, Domenico Giovanni Della Rocca, Carola Gianni, J David Burkhardt, G Joseph Gallinghouse, Patrick Hranitzky, Amin Al-Ahmad, Luigi Di Biase, Shane Bailey, Rodney Horton, Andrea Natale
Journal: Circulation (2018)

Introduction: Left atrial appendage occlusion is a potential alternative especially in those intolerant or not suitable for long-term oral anticoagulation therapy. Hypothesis: To evaluate the assoc...
Sarita Rai Gurung
Authors: Ashish Gurung
Journal: BMJ (2020)

Sarita Rai Gurung moved to the UK in 2004 to start as a clinical observer in paediatrics at the Hull Royal Infirmary. She had a great love for children, having worked in Kanti Children’s Hospital in Kathmandu, Nepal. In the UK, she continued to work in Hull …
Functional respiratory imaging repurposed for COVID-19
Authors: Josien van Es, Lilian J Meijboom
Journal: Thorax (2020)

Thillai and colleagues 1 describe a method of image analysis, functional respiratory imaging (FRI), which creates a threedimensional reconstruction of both airways and the pulmonary vasculature from CT-scan images, in 10 patients with severe COVID-19 infection.They computed the distribution of pulmonary blood flow according cross-sectional vessel area size and compared the data to age, gender, height and premorbidity matched acute respiratory distress syndrome (ARDS) patients (n=7) and retrospective data from healthy volunteers (n=107).Their post processing imaging results were interesting as they find that in patients with COVID-19, the blood flow was diminished in the peripheral small calibre vessels and conversely increased in the more centrally located arteries in comparison to both the ARDS and the healthy control group, without differences in right ventricular size.These data are currently hypothesis generating rather than a basis for clinical interpretations or even therapeutical changes on the current treatment protocol.The authors postulated that the impaired gas exchange seen in COVID-19 may be explained by redistribution due to either micro-thrombi, vasoconstriction of distal pulmonary arteries, or both.Indeed, in patients with COVID-19 admitted on the intensive care unit, the prevalence of (micro)thrombi is unexpectedly high and the prevalence of bacterial and fungal superinfections, in which you might expect secondary vasoconstriction is also considerable, 31% versus 7.2%, respectively.
Nitrogen-doped fluorescence carbon dots as multi-mechanism detection for iodide and curcumin in biological and food samples
Authors: Xiaodan Tang, Hongmei Yu, Brian Bui, Lingyun Wang, Christina Xing, Shaoyan Wang, Mingli Chen, Zhizhi Hu, Wei Chen
Journal: Bioactive Materials (2020)

Iodine ion is one of the most indispensable anions in living organisms, particularly being an important substance for the synthesis of thyroid hormones. Curcumin is a yellow-orange polyphenol compound derived from the rhizome of
Value-Based Insurance Design in Cardiology: Using “Clinical Nuance” to Improve Quality of Care and Contain Costs⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Eric C. Stecker, Eric M. Riles, A. Mark Fendrick
Journal: Journal of the American College of Cardiology (2012)
Long-Term Therapy With Organic Nitrates: The Pros and Cons of Nitric Oxide Replacement Therapy**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Tommaso Gori, John D. Parker
Journal: Journal of the American College of Cardiology (2004)
14248 Efficacy and safety trends with continuous long-term use of 2% crisaborole ointment in patients with mild to moderate atopic dermatitis
Authors: Mark G. Lebwohl, Adelaide A. Hebert, Liza Takiya, Lauren E. Miller, John L. Werth, Chuanbo Zang, Paul Sanders, Bob Geng
Journal: Journal of the American Academy of Dermatology (2020)
Characteristics of cytokines in the sciatic nerve stumps and DRGs after rat sciatic nerve crush injury
Authors: Rui-Rui Zhang, Sai-Ling Chen, Zhang-Chun Cheng, Yin-Ying Shen, Sheng Yi, Hui Xu
Journal: Military Medical Research (2020)

Cytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators after peripheral nerve injury are still unclear. This study aimed to identify cytokines critical for the regenerative process of injured peripheral nerves. The sequencing data of the injured nerve stumps and the dorsal root ganglia (DRGs) of Sprague-Dawley (SD) rats subjected to sciatic nerve (SN) crush injury were analyzed to determine the expression patterns of genes coding for cytokines. PCR was used to validate the accuracy of the sequencing data. A total of 46, 52, and 54 upstream cytokines were differentially expressed in the SNs at 1 day, 4 days, and 7 days after nerve injury. A total of 25, 28, and 34 upstream cytokines were differentially expressed in the DRGs at these time points. The expression patterns of some essential upstream cytokines are displayed in a heatmap and were validated by PCR. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved. In summary, these findings provide an overview of the dynamic changes in cytokines in the SNs and DRGs at different time points after nerve crush injury in rats, elucidate the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses after peripheral nerve injury, and thus might contribute to the identification of potential treatments for peripheral nerve repair and regeneration.
Stem cell therapy for myocardial repair: Is it arrhythmogenic?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Raj R Makkar, Michael Lill, Peng-Sheng Chen
Journal: Journal of the American College of Cardiology (2003)
Abstract 344: The Association Between ALS Response Interval and Out-of Hospital Cardiac Arrest Outcomes
Authors: Brian Grunau, Takahisa Kawano, John Tallon, Frank Scheuermeyer, Joshua Reynolds, Floyd Besserer, David Barbic, Steven Brooks, Ron Straight, Jim Christenson
Journal: Circulation (2018)

Objective: There is conflicting data in studies investigating the effectiveness of advanced life support (ALS) for out-of-hospital cardiac arrest (OHCA). Within a tiered BLS-ALS system, we sought to determine if the ALS response interval was associated with patient outcomes. Methods: This secondary analysis examined prospectively identified consecutive non-traumatic adult OHCAs from 2006-2016 in British Columbia. We excluded EMS-witnessed arrests and those not treated by ALS. The primary and secondary outcomes were survival and favorable neurological outcomes (mRS ≤3) at hospital discharge. Using logistic regression we estimated the association of ALS response interval (9-1-1 call to ALS arrival) and outcomes, adjusting for treatment year, response interval of the first EMS unit, and other baseline characteristics. We drew spline curves to illustrate this relationship. Results: Of 12,722 included cases, survival was 12%. The median response interval for the first EMS unit was 6.4 minutes (IQR 5.2 - 8.3) and for ALS was 11.8 minutes (IQR 8.7 - 16.5).The adjusted odds of survival and favourable neurological outcome for each additional minute in ALS response interval were 0.98 (95 % CI 0.96-0.99) and 0.98, (95% CI 0.97-0.99) respectively. The spline curve demonstrated an initial decline in survival probability that moderated at approximately 11 minutes. Conclusion: Among ALS-treated subjects within our tiered EMS system, earlier ALS arrival was associated with improved survival and favorable neurological outcomes. The greatest yield of ALS care may be prior to 11 minutes. This may help inform the optimal deployment configuration of prehospital providers.
SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery
Authors: Siwen Hu-Lieskovan, Srabani Bhaumik, Kavita Dhodapkar, Jean Charles J.B. Grivel, Sumati Gupta, Brent A. Hanks, Sylvia Janetzki, Thomas O. Kleen, Yoshinobu Koguchi, Amanda W. Lund, Cristina MacCalli, Yolanda D. Mahnke, Ruslan D. Novosiadly, Senthamil R. Selvan, Tasha Sims, Yingdong Zhao, Holden T. Maecker
Journal: Journal for ImmunoTherapy of Cancer (2020)

Since the publication of the Society for Immunotherapy of Cancer's (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients.
Reconsidering Named Honorifics in Medicine—the Troubling Legacy of Dermatologist Albert Kligman
Authors: Adewole S. Adamson, Jules B. Lipoff
Journal: JAMA Dermatology (2020)

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 Dermatology 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 Dermatology journal
Cover Image: Boron neutron capture therapy: Current status and future perspectives
Authors: Mayya Alexandrovna Dymova, Sergey Yurjevich Taskaev, Vladimir Alexandrovich Richter, Elena Vladimirovna Kuligina
Journal: Cancer Communications (2020)

The cover image is based on the Review Article Boron neutron capture therapy: current status and future perspectives by Maya Dymova et al., https://doi.org/10.1002/cac2.12089.
13065 More moderate levels of disease severity at baseline related to achievement of treatment targets with apremilast: Results from a pooled analysis
Authors: Mark Lebwohl, Ulrich Mrowietz, M. Alan Menter, Christopher E.M. Griffiths, Jerry Bagel, Natalie Núnez Gómez, Rui Shi, Rebecca Shi, Benoit Guerette, Eugenia Levi, Kristian Reich
Journal: Journal of the American Academy of Dermatology (2020)
16958 Frequent symptomatic and emotional struggles impact all aspects of quality of life in patients with psoriasis: A qualitative study
Authors: Vanina Taliercio, Lisa Webber, Adelheid Langner, Bianca E. Rich, Abram Beshay, Dominik Ose, Rachel Hess, Jamie L.W. Rhoads, Aaron Secrest
Journal: Journal of the American Academy of Dermatology (2020)