tbuckley/cabot-search huggingface dataset:
Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles
Authors: Tianmu Hu, Anwar Saeed Ahmed Qahtan, Lei Lei, Zhixin Lei, Dapeng Zhao, Hemin Nie
Journal: Bioactive Materials (2017)

In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant (p > 0.05). In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.
Impact of Liraglutide on Amylase, Lipase, and Acute Pancreatitis in Participants With Overweight/Obesity and Normoglycemia, Prediabetes, or Type 2 Diabetes: Secondary Analyses of Pooled Data From the SCALE Clinical Development Program
Authors: William M. Steinberg, Julio Rosenstock, Thomas A. Wadden, Morten Donsmark, Christine B. Jensen, J. Hans DeVries
Journal: Diabetes Care (2017)

To describe amylase/lipase activity levels and events of acute pancreatitis (AP) in the SCALE (Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes) weight-management trials.Secondary analyses were performed on pooled data from four trials (N = 5,358 with BMI ≥30, or 27 to <30 kg/m2 with ≥1 comorbidity). Of these, 1,723 had normoglycemia, 2,789 had prediabetes, and 846 had type 2 diabetes. Participants were randomized to liraglutide 3.0 mg (n = 3,302), liraglutide 1.8 mg (n = 211, only type 2 diabetes), or placebo (n = 1,845). Relationships between baseline characteristics and amylase/lipase activity at baseline and during treatment were investigated.Over 56 weeks, liraglutide 3.0 mg versus placebo was associated with increases in mean levels of 7% (amylase) and 31% (lipase), respectively. Similar changes in amylase/lipase levels were observed with liraglutide 1.8 mg. More participants receiving liraglutide 3.0 mg versus placebo experienced amylase (9.4% vs. 5.9%) and lipase (43.5% vs. 15.1%) elevations greater than or equal to the upper limit of normal (ULN); few had elevations ≥3 × ULN for amylase (<0.1% with liraglutide 3.0 mg or placebo) or lipase (2.9% vs. 1.5%, respectively). After liraglutide discontinuation, enzymes returned to baseline levels. Thirteen participants developed AP: 12 on (n = 9, 0.3%) or after (n = 3, 0.1%) liraglutide 3.0 mg treatment and one (0.1%) with placebo. A total of 6/13 participants with AP (5/12 liraglutide; 1 placebo) had gallstone disease evident at AP onset. Amylase/lipase elevations either 1 × ULN or ≥3 × ULN before AP onset had very low positive predictive value for AP (<1%).Liraglutide resulted in dose-independent, reversible increases in amylase/lipase activity, unrelated to baseline characteristics, not predicting AP onset. Gallstones possibly contributed to 50% of AP cases. Data provide no basis for amylase/lipase level monitoring in liraglutide treatment except in suspected AP.
Addressing Bias and Conflict of Interest Among Biomedical Researchers
Authors: Lisa Bero
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 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
Clarification of Clinical Trial Registration and Reported Study Outcomes
Authors: Patrick A. Resick, Jennifer Schuster Wachen, Alan L. Peterson
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy
Authors: Azael Freites-Martinez, Bernice Y. Kwong, Kerri E. Rieger, Daniel G. Coit, A. Dimitrios Colevas, Mario E. Lacouture
Journal: JAMA Dermatology (2017)

To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab.To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management.Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs.All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery.Three consecutive patients with cancer, 2 men and 1 woman (median age, 83 years; range 77-91 years), experienced pembrolizumab-associated eruptive KAs. All patients presented with a sudden onset of multiple lesions on sun-exposed areas of their extremities after a median of 13 months (range, 4-18 months) of pembrolizumab therapy. On lesional biopsy, a lichenoid infiltrate was observed in the underlying dermis, predominantly composed of CD3+ T cells, scattered CD20+ B cells, and relatively few PD-1+ (programmed cell death 1-positive) T cells, an immunophenotypic pattern also observed in other cases of anti-PD-1-induced lichenoid dermatitis. Patients were treated with clobetasol ointment and intralesional triamcinolone, alone or in combination with open superficial cryosurgery. All KAs resolved in all patients, and no new lesions occurred during close follow-up. Pembrolizumab treatment was continued without disruption in all 3 cases, and all patients had complete responses of their primary cancers.Pembrolizumab is used in advanced melanoma, advanced non-small-cell lung cancer, and in head and neck cancer. A variety of dermatologic immune-related adverse events including maculopapular eruption, lichenoid reactions, pruritus, and vitiligo have been described. This case series demonstrates that pembrolizumab therapy may also be associated with eruptive KAs with characteristic dermal inflammation, which improved with corticosteroid treatment (topical and intralesional) alone or in combination with cryosurgery, allowing patients to continue therapy with pembrolizumab.
OVERUSE PROBLEMS IN ICELANDIC MALE HANDBALL
Authors: Elis Thor Rafnsson, Grethe Myklebust, Roald Bahr, Anna Frohm, Ornolfur Valdimarsson, Arni Arnason
Journal: British Journal of Sports Medicine (2017)

Background The majority of studies in handball register only time loss injuries. From previous studies and our experience working with handball players we know that playing with overuse problems are common and such symptoms can affect their performance. Objective To register the prevalence of overuse problems in low back, knee and dominant shoulder among Icelandic male handball players using questionnaire designed by OSTRC in Oslo, Norway. Design Prospective cohort study. Players from the two highest division in Iceland were invited. Setting Icelandic elite male handball players. Patients (or Participants) Out of 14 elite male handball teams invited, totally 229 players from 13 teams participated. The first questionnaire was answered by 206 players; 137 answered the final one. Interventions (or Assessment of Risk Factors) The questionnaire was distributed sixteen times to players via e-mail, every second week from September 25th 2012 to April 22nd 2013. Main Outcome Measurements The prevalence of overuse problems (every problems registered) and substantial problems (problems affecting performance or participation) were calculated for knee, low back and dominant shoulder. This was done for each questionnaire by dividing the number of players that reported problems (overuse or substantial overuse) by the total number of respondents. Results The response ratio was 71.5%. During the research period 91% of participants reported overuse problems and 61% reported substantial overuse problems. The average prevalence of overuse problems was 34% (31–37 95% CI), varying from 21–47%, highest during the pre-season period (September 25th to October 8th). The average prevalence of substantial overuse problems was 12% (10–14 95% CI), varying from 6–15% over the research period. Conclusions Substantial overuse problems are constantly affecting many players during the season. High prevalence in the first two questionnaires raises speculations about the training methods during the pre-season.
The results of changes in treatment strategy in Russian women with breast cancer stage I: Long-time experience.
Authors: Irina Vladimirovna Kolyadina, Irina Poddubnaya, G. Frank, A. Karseladze, Dmitry Komov
Journal: Journal of Clinical Oncology (2015)

e11541 Background: the differences in treatment and recurrence-free (RFS) and cancer-specific (CSS) survival in Russian women with breast cancer stage I during last 25 years. Methods: In our study included 1341 women with breast cancer stage I treated in RCRC and RMAPE 1985-2012. We analyzed the clinical, morphological data, type of therapy in different time-period ( < 1995; 1996-1999; 2000-2004; 2005-2009; > 2010) and prognostic value these factors for RFS and CSS (median follow-up - 96 month). Results: Patients with breast cancer stage I treated < 2000 used adjuvant system therapy (endocrinotherapy, chemotherapy or both) only in 24% cases. In contrast to this, women treated > 2000 used adjuvant system therapy in 61% (2000-2004), in 85% (2005-2009) and in 91% ( > 2010), p < 0,0001. As result, 5- and 10-years RFS in women treated < 2000 was 71 and 61% only, and in patients treated > 2000 was 93 and 89%, p < 0,0001. The same data we saw in 5- and 10-years CSS: in women treated < 2000 was 87 and 75% only, in patients treated > 2000 was significant higher (98 and 95%), p < 0,0001. In multivariate analyze for prognostic value of different clinical and morphological factors for RFS and CSS only two factors were significant (p < 0,05): biological subtype and adjuvant system therapy. The most favorable was luminal A subtype (5- and 8-years RFS was 97 and 94%; 5- and 8-years CSS was 99 and 94%). In compare with luminal A subtype the risk of recurrences was significant higher in luminal B subtypes (HR 1,393), in triple negative cancer (HR 2,297) and ER-PR-HER2+ subtype (HR 6,001), p = 0,04. Adjuvant system therapy significantly reduced the risk of recurrence (HR = 0,276, p < 0,001). In compare with luminal A subtype the risk of death from cancer was significant higher in luminal B subtype (HR 1,466), triple-negative cancer (HR 4,269) and in ER-PR-HER2+ subtype (HR 7,477), p = 0,049. Adjuvant system therapy significantly reduced the risk of death from cancer too (HR 0,234, p = 0,023). Conclusions: Adjuvant system therapy according to tumor biology became the standard treatment in women with breast cancer stage I after 2000 and significantly improved RFS and CSS.
SAK-HV Triggered a Short-period Lipid-lowering Biotherapy Based on the Energy Model of Liver Proliferation via a Novel Pathway
Authors: Chao Zhang, Zhiguang Huang, Haoran Jing, Wenliang Fu, Min Yuan, Wenrong Xia, Ling Cai, Xiangdong Gan, Yao Chen, Minji Zou, Minhui Long, Jiaxi Wang, Min Wang, Donggang Xu
Journal: Theranostics (2017)

The accumulations of excess lipids within liver and serum are defined as non-alcoholic fatty liver disease (NAFLD) and hyperlipemia respectively. Both of them are components of metabolic syndrome that greatly threaten human health. Here, a recombinant fusion protein (SAK-HV) effectively treated NAFLD and hyperlipemia in high-fat-fed ApoE-/- mice, quails and rats within just 14 days. Its triglyceride and cholesterol-lowering effects were significantly better than that of atorvastatin during the observation period. We explored the lipid-lowering mechanism of SAK-HV by the hepatic transcriptome analysis and serials of experiments both in vivo and in vitro. Unexpectedly, SAK-HV triggered a moderate energy and material-consuming liver proliferation to dramatically decrease the lipids from both serum and liver. We provided the first evidence that PGC-1α mediated the hepatic synthesis of female hormones during liver proliferation, and proposed the complement system-induced PGC-1α-estrogen axis via the novel STAT3-C/EBPβ-PGC-1α pathway in liver as a new energy model for liver proliferation. In this model, PGC-1α ignited and fueled hepatocyte activation as an "igniter"; PGC-1α-induced estrogen augmented the energy supply of PGC-1α as an "ignition amplifier", then triggered the hepatocyte state transition from activation to proliferation as a "starter", causing triglyceride and cholesterol-lowering effects via PPARα-mediated fatty acid oxidation and LDLr-mediated cholesterol uptake, respectively. Collectively, the SAK-HV-triggered distinctive lipid-lowering strategy based on the new energy model of liver proliferation has potential as a novel short-period biotherapy against NAFLD and hyperlipemia.
Epigenetic Mechanisms Regulating Adaptive Responses to Targeted Kinase Inhibitors in Cancer
Authors: Steven P. Angus, Jon S. Zawistowski, Gary L. Johnson
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance. In addition to genomic resistance mechanisms, adaptive transcriptional and signaling responses seen in tumors are gaining appreciation as alterations that lead to a phenotypic state change-often observed as an epithelial-to-mesenchymal shift or reversion to a cancer stem cell-like phenotype underpinned by remodeling of the epigenetic landscape. This epigenomic modulation driving cell state change is multifaceted and includes modulation of repressive and activating histone modifications, DNA methylation, enhancer remodeling, and noncoding RNA species. Consequently, the combination of kinase inhibitors with drugs targeting components of the transcriptional machinery and histone-modifying enzymes has shown promise in preclinical and clinical studies. Here, we review mechanisms of resistance to kinase inhibition in cancer, with special emphasis on the rewired kinome and transcriptional signaling networks and the potential vulnerabilities that may be exploited to overcome these adaptive signaling changes.
A Randomized Phase 2 Placebo Controlled Trial of Clobetasol Rinse for Treatment of Oral Chronic Graft-Versus-Host Disease
Authors: Jacqueline W. Mays, Lauren M. Curtis, Carol Bassim, Seth M. Steinberg, David Venzon, Jeremy J. Rose, Monica Cho, Christopher G. Kanakry, Fahd Yazdanie, Daniele Avila, Kristin Baird, Jennifer Hsu, Licia Masuch, George Grimes, Judith Starling, Daniel H. Fowler, Ronald E. Gress, Fran T. Hakim, Steven Z. Pavletic
Journal: Blood (2016)
Quality and Safety in Health Care, Part XXVIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2017)

The biggest registry of its kind for pediatric and congenital heart operations on earth is the Congenital Heart Surgery Database of the Society of Thoracic Surgeons. This article discusses the history, current status, and contributions of the Congenital Heart Surgery Database to quality, safety, and research. Its data have implications not only for patient care after surgery, but also for estimating patient risk of surgery and for health care economics.
Clinical significance of CD73 expression in triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial
Authors: L. Buisseret, S. Pommey, B. Allard, S. Garaud, L. Ameye, A. Di Leo, J.P.A. Crown, M. Piccart-Gebhart, C. Sotiriou, J. Stagg
Journal: Annals of Oncology (2017)
Advanced Analgesic Drug Delivery and Nanobiotechnology
Authors: Nicoleta Stoicea, Juan Fiorda-Diaz, Nicholas Joseph, Muhammad Shabsigh, Carlos Arias-Morales, Alicia A. Gonzalez-Zacarias, Ana Mavarez-Martinez, Stephen Marjoribanks, Sergio D. Bergese
Journal: Drugs (2017)

Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.
Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial
Authors: Sobha Sivaprasad, A Toby Prevost, Joana C Vasconcelos, Amy Riddell, Caroline Murphy, Joanna Kelly, James Bainbridge, Rhiannon Tudor-Edwards, David Hopkins, Philip Hykin, A Bhatnagar, B Burton, U Chakravarthy, H Eleftheriadis, T Empeslidis, R Gale, S George, M Habib, S Kelly, A Lotery, M McKibbin, L Membrey, G Menon, B Mushtaq, L Nicholson, J Ramu, O Osoba, J Patel, P Prakash, R Purbrick, A Ross, A Stylianides, J Talks, U Chakravarthy, S Harding, T Peto, S T Yeo, Alistair Laidlaw, Winfried Amoaku, Gillian Hood, Graham A Hitman, Daniel Preece, Paul Burns, Sarah Walker, Evelyn Mensah, Niral Karia
Journal: The Lancet (2017)
Desiccating stress worsens alkali burn injury by magnifying caspase-8-induced imbalance of NLRP3 and NLRP6
Authors: Xia Hua, Xiaoyong Yuan, Yonghao Li, Hui Chen, Jin Yuan, Silvia Tanumiharjo, Fang Bian, Lishi Su, Yanhua Hong, Yizhi Liu, Wei Chi
Journal: Journal of Allergy and Clinical Immunology (2017)
Impact of Asian American race on prostate cancer outcomes
Authors: S. A. Brassell, E. Raymundo, Y. Chen, J. Zhao
Journal: Journal of Clinical Oncology (2009)

5165 Background: The global increased incidence of prostate cancer (CaP) is of growing concern, notably in Asia where a 118% rise has been documented. Recent publications report that Asian Americans are more likely to have advanced clinical stage, higher tumor grades, and worse survival rates compared to other racial groups. It remains unclear if these adverse outcomes are attributable to intrinsic biologic differences of CaP in Asians or socioeconomic and cultural differences. Methods: Men registered into the Center for Prostate Disease Research multi-center military national database from 1989–2007 with biopsy-proven CaP and categorized as Asian American, Caucasian, or African American descent were included. Demographic and clinical characteristics were examined. Frequencies were reported for categorical features. Measures of central tendency and dispersion were reported for continuous features. Chi-square, ANOVA and Kruskal-Wallis test were used to examine association between race and clinico-pathologic features. Differences of PSA recurrence and overall survival rates were analyzed by Kaplan-Meier. The multi-variate Cox proportional hazard model was used to examine predictive value of clinico-pathologic features. Results: Included patients were 10,964: 583 (5.3%) Asian Americans, 2,046 (18.7%) African Americans, and 8,335 (76.0%) Caucasians. At diagnosis, Asian Americans had lower clinical stage (p&lt;0.0001) but worse biopsy grade (p = 0.0006) than other groups. They had a higher percentage of organ confined disease (p &lt; 0.0001) and were more likely to choose radical prostatectomy (RP) (p &lt; 0.0001). Asian Americans had improved biochemical recurrence free (p&lt;0.01) and overall survival (p &lt; 0.001) compared to African Americans or Caucasians treated with RP or external beam radiation. Conclusions: Asian Americans with CaP treated in an equal access military health care system have improved pathologic outcomes and survival characteristics compared with other races. Asian ethnicity's negative impact on survival noted by others appears to be from factors other than the tumor's intrinsic behavior such as language barriers, socioeconomic status, and cultural norms. No significant financial relationships to disclose.