tbuckley/cabot-search huggingface dataset:
Protein Corona Liposomes Achieve Efficient Oral Insulin Delivery by Overcoming Mucus and Epithelial Barriers
Authors: Aohua Wang, Tiantian Yang, Weiwei Fan, Yiwei Yang, Quanlei Zhu, Shiyan Guo, Chunliu Zhu, Yongchun Yuan, Tao Zhang, Yong Gan
Journal: Advanced Healthcare Materials (2018)

Oral delivery of peptide/protein drugs has attracted worldwide attention due to its good patient compliance and convenience of administration. Orally administered nanocarriers always encounter the rigorous defenses of the gastrointestinal tract, which mainly consist of mucus and epithelium barriers. However, diametrically opposite surface properties of nanocarriers are required for good mucus penetration and high epithelial uptake. Here, bovine serum albumin (BSA) is adsorbed to cationic liposomes (CLs) to form protein corona liposomes (PcCLs). The aim of using PcCLs is to conquer the mucus and epithelium barriers, eventually improving the oral bioavailability of insulin. Investigations using in vitro and in vivo experiments show that the uptake amounts and transepithelial permeability of PcCLs are 3.24- and 7.91-fold higher than that of free insulin, respectively. Further study of the behavior of PcCLs implies that BSA corona can be shed from PcCLs as they cross the mucus layer, which results in the exposure of CLs to improve the transepithelial transport. Intrajejunal administration of PcCLs in type I diabetic rats produces a remarkable hypoglycemic effect and increases the oral bioavailability up to 11.9%. All of these results imply that PcCLs may provide a new insight into the method for oral insulin delivery by overcoming the multiple barriers.
Venetoclax with Low-Dose Cytarabine Induces Rapid, Deep, and Durable Responses in Previously Untreated Older Adults with AML Ineligible for Intensive Chemotherapy
Authors: Andrew Wei, Stephen A. Strickland, Jing-Zhou Hou, Walter Fiedler, Tara L Lin, Roland B. Walter, Anoop K Enjeti, Wan-Jen Hong, Brenda Chyla, Relja Popovic, Kaffa Fakouhi, Tu Xu, John Hayslip, Gail J. Roboz
Journal: Blood (2018)
A Phase II Study of Tumor-infiltrating Lymphocyte Therapy for Human Papillomavirus–associated Epithelial Cancers
Authors: Sanja Stevanović, Sarah R. Helman, John R. Wunderlich, Michelle M. Langhan, Stacey L. Doran, Mei Li M. Kwong, Robert P.T. Somerville, Christopher A. Klebanoff, Udai S. Kammula, Richard M. Sherry, James C. Yang, Steven A. Rosenberg, Christian S. Hinrichs
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Cellular therapy is an emerging cancer treatment modality, but its application to epithelial cancers has been limited. This clinical trial evaluated tumor-infiltrating lymphocyte (TIL) therapy for the treatment of patients with metastatic human papillomavirus (HPV)-associated carcinomas. Patients and Methods: The trial was a phase II design with two cohorts, cervical cancers and noncervical cancers. Cell infusion was preceded by a lymphocyte-depleting conditioning regimen and followed by systemic high-dose aldesleukin. Results: Objective tumor responses occurred in 5 of 18 (28%) patients in the cervical cancer cohort and 2 of 11 (18%) patients in the noncervical cancer cohort. Two of the responses in cervical cancer were complete and are ongoing 67 and 53 months after treatment. Responses in the noncervical cancer cohort were in anal cancer and oropharyngeal cancer. The HPV reactivity of the infused T cells correlated with clinical response. Peripheral blood repopulation with HPV-reactive T cells also correlated with clinical response. Conclusions: These findings support the concept that cellular therapy can mediate the regression of epithelial cancers, and they suggest the importance of predictive biomarkers and novel treatment platforms for more effective therapies.
Abstract #3656: The BH3 alpha helical mimic BH3M-6 disrupts Bcl-xL/Bax and Mcl-1/Bax binding and induces apoptosis in human cancer cells in a Bcl-xL, Bcl2 and Mcl-1 dependent manner.
Authors: Aslamuzzaman Kazi, Jiazhi Sun, Hang Yin, Andrew Hamilton, Hong-Gang Wang, Said Sebti
Journal: Cancer Research (2009)

Evasion of apoptosis is a critical malignancy hallmark that is required for cancer cell survival. One mechanism by which tumor cells evade apoptosis is by overexpressing tumor survival proteins such as those of the Bcl family, which bind to the alpha helical BH3 domain of pro-apoptotic proteins such as Bax, Bim, and Bad. We designed a BH3 alpha helical mimic BH3M-6 which binds Bcl-xL and prevents its binding to Bax in vitro with an IC50 value of 750 nM using a fluorescence polarization assay. GST pulldown assays also demonstrated that BH3M-6 inhibits Bcl-xL/Bax and Mcl-1/Bax binding. Furthermore, using co-immunoprecipitation, cytosolic redistribution of mitochondrial GFP-Bad as well as Bimolecular Fluorescence Complementation assays we demonstrated that BH3M-6 inhibits in intact cells the binding of Bcl-xL to Bax, Bad and Bim. BH3M-6 induced cytochrome c release, capase 3 activation and PARP degradation. Finally, in human cancer cells that depend on the Bcl family members for survival, BH3M-6 induced apoptosis in a Bcl-Xl, Bcl-2 and Mcl-1-dependent manner.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3656.
Aggressive genomic features in clinically indolent primary HHV8-negative effusion-based lymphoma
Authors: Matias Mendeville, Margaretha G. M. Roemer, Mari F. C. M. van den Hout, G. Tjitske Los-de Vries, Reno Bladergroen, Phylicia Stathi, Nathalie J. Hijmering, Andreas Rosenwald, Bauke Ylstra, Daphne de Jong
Journal: Blood (2018)
What is unified validity theory and how might it contribute to research and practice with athlete self-report measures
Authors: Johann Windt, David Taylor, Dustin Nabhan, Bruno D Zumbo
Journal: British Journal of Sports Medicine (2018)

Athlete self-report measures (ASRMs) are an extremely popular athlete monitoring tool in professional sports.1 Their popularity stems from their ease of use, low/no cost, and a growing body of literature that highlights that ASRMs are more sensitive to injury/illness risk than many physiological biomarkers.2 Whether ASRMs are used to examine athletes’ data once (eg, preseason baseline testing) or to regularly monitor athletes over time (eg, daily or weekly), the results are often used to drive decision-making and load management in elite sport. However, these decisions may be flawed if inappropriate conclusions are reached. When sports medicine practitioners decide on an ASRM, tensions may exist between practical, short, custom solutions and generally longer, scientifically ‘validated’ surveys. In this editorial, we introduce unified validity theory and discuss how it might ease this tension.

Athlete engagement is a challenge in applied sport settings, and athletes report that the time it takes to complete surveys is a barrier to ASRM use.3 The more comprehensive the measure, the longer it takes for athletes to complete, and the lower the uptake. This has led to a plethora of ‘bespoke’, short surveys/questionnaires used in applied practice that often resemble the items (eg, sleep quality, stress, fatigue and muscle soreness) in the original work by Hooper et al .4 

As ASRMs continued to rise in popularity, academic discussions brought validity considerations to the forefront—calling researchers to use …
Coordinating Clinical Trials to Confirm Drug Safety and Efficacy—Resolving Uncertainty
Authors: Joseph S. Ross
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Electronic medical records: lengthy, inaccurate, and meaningless
Authors: Pablo Millares Martin
Journal: BMJ (2018)

General practitioners and NHS organisations undoubtedly relate differently to electronic medical records.1 Some are good, coding most activity, innovating, analysing, focusing on progress. Some are bad, coding data mainly for financial purposes (like quality and outcomes frameworks), leaving plenty of information as free text or not properly coded, thus negating a …
AB0375 A systematic literature review of omega 3 in the treatment of rheumatoid arthritis
Authors: M. Prince, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Many different elements and variations of diet in the management of rheumatoid arthritis (RA) have been studied over the years such as vegan or Mediterranean diets. <h3>Objectives</h3> This systematic literature review covers one food stuff, omega-3 polyunsaturated fats efficacy in the management of RA alongside or independent of conventional DMARD therapy. <h3>Methods</h3> A systematic review of the literature between 1966–2017 was conducted using MEDLINE, CINAHL and EMBASE databases, with key words "RA" and "omega-3" for English-language articles producing 209 hits. We then refined to publications within the last 10 years, giving 96 results. Only including clinical trials gave 12 hits pertaining to 8 trials. <h3>Results</h3> The table above shows a summary of the evidence found. In total, 751 were exposed to omega-3 versus 1733 controls with the smallest study being an RCT involving 13 people and the largest a case-control study with 1569 participants. A notable difference between these studies was the use of DMARD therapy as part of the inclusion or exclusion criteria. Another difference noted was the RA stage eligible for a trial. Some studies required a diagnosis of RA of &lt;12 months whereas most required stable RA ongoing for &gt;12 months. <h3>Conclusions</h3> This review concludes that omega-3 leads to clinical and statistically significant improvements in RA. There was a significant heterogeneity in the trials published with different inclusion criteria especially regarding disease duration and concomitant DMARD therapy. It would seem prudent to include dietary advice in our advice to patients when treating RA. Possible reasons for this evidence would include altering the microbiome. <h3>References</h3> [1] The British Journal of Nutrition2015;114(6):885–90. [2] Epidemiology1996;7(3):256–63. [3] Archives of Medical Research2012;43(5):356–62. [4] Journal of Parenteral and Enteral Nutrition2010;34(2):151–5. [5] Global Journal of Health Science2015;8(7):18. [6] Arthritis Care &amp; Research2017. [7] Rheumatology (Oxford, England)2008;47(5):665–9. [8] Nutrients2017;9(4). <h3>Disclosure of Interest</h3> None declared
Prognostic understanding and barriers to palliative care in patients with metastatic lung cancer on immunotherapy.
Authors: Laurie Steffen, Thomas Lycan, Beverly J Levine, Jennifer Gabbard, Jimmy Ruiz, Stefan C. Grant, A. William Blackstock, Kathryn E. Weaver, William J. Petty
Journal: Journal of Clinical Oncology (2018)

36 Background: Communicating prognosis and integrating palliative care (PC) are challenging yet vital aspects of quality care for patients with metastatic non-small cell lung cancer (NSCLC). These tasks may be more difficult in the setting of immunotherapy, as this modality may offer a durable response but only in 10-20% of patients. Our goal was to identify correlates of prognostic understanding and interest in PC among stage IV NSCLC patients receiving immunotherapy. Methods: We conducted a cross-sectional survey of 60 patients (M age = 62.5 years; SD = 9.3 years; 40% male; 45% ≤ high school degree; 68% ECOG ≤ 1) undergoing immuno- or chemo-immunotherapy for stage IV NSCLC (80% de novo) at an academic medical center. Results: Most patients (73%) reported that knowing their prognosis was very important. Nearly all said the goal of treatment was to help them live longer (98%), feel better (95%), and completely rid them of cancer (85%); 49% thought they were likely to be cured. Only 17% of patients were interested in meeting with PC; 12% had been referred. Those patients with worse performance status (PS; ECOG 2-3) (79% vs. 35%, p = .002) and who had not yet had an appointment to assess treatment response (67% vs. 37%, p = .03) were more likely to believe they would be cured. There were no differences in expectation based on treatment response, time since diagnosis, de novo versus recurrent metastatic disease, or health literacy level. Interest in meeting with PC did not significantly differ based on expectation for cure, though only 13% of those who thought a cure was unlikely were interested in PC compared to 21% who thought a cure was likely. Patients noted multiple barriers to PC, including preference for self-management (58%), lack of provider recommendation (47%), misconceptions (e.g., PC is for people about to die; 45%), and access barriers [e.g., time (36%) and cost (24%)]. Conclusions: Many patients receiving immunotherapy for stage IV NSCLC may expect curative treatment even when they are not actually responding or have poor performance status. Efforts to improve palliative care literacy and use in this population should address PC misconceptions and emphasize its role, including how it can support self-management.
How Strong Is the Evidence to Support Blood Pressure Treatment Goal of 130/80 mm Hg?
Authors: Sanjay Kaul
Journal: Circulation (2018)

he 2017 American College of Cardiology/American Heart Association guideline for the prevention, detection, evaluation, and management of high blood pressure (BP) in adults is the first comprehensive hypertension clinical practice guideline since 2003. 1 The guideline document comprises 111 pages, 11 figures, 448 data tables, and 1000 references covering 106 recommendations (113 by my count).Only 8% (10 of 113) are supported by high-level evidence (Class I, Level of Evidence A recommendations); 36% (31 of 113) are based on Class II recommendations (22% [25 of 113] Class IIa, 14% [16 of 113] Class IIb) consistent with equivocal evidence; and 44% (50 of 113) are based on Level of Evidence C recommendations driven primarily by expert opinion.Notably, there were 8 Class I, Level of Evidence C recommendations supporting a diastolic BP goal of <80 mm Hg, for which there is little to no supporting evidence.One of the most controversial recommendations in the new guideline is the BP treatment goal of <130/80 mm Hg across a wide spectrum of risk or comorbidities.The guideline development group conducted a structured review of the literature and commissioned a systematic review and meta-analysis from an independent Evidence Review Committee to address the optimal target for BP lowering during antihypertensive therapy. 2 For the specific evaluation of a systolic BP target <130 mm Hg compared with any higher BP target, 9 studies were identified.Data were pooled via the random-effects meta-analysis with the DerSimonian-Laird method.The key results are reproduced in the Table.The review committee concluded the following: SBP [systolic BP] lowering to <130 mm Hg significantly reduced the risk of major cardiovascular events (RR [risk reduction]: 0.84; 95% CI: 0.73-0.99)and stroke (RR: 0.82; 95% CI: 0.70-0.96)and risk reductions remained "marginally" significant for MI [myocardial infarction] (RR: 0.85; 95% CI: 0.73-1.00)and all-cause mortality (RR: 0.92; 95% CI: 0.79-1.06).Heterogeneity between studies was lowest for MI, stroke, and renal events and highest for major cardiovascular events and heart failure although it was not statistically significant. 2There are several limitations of this meta-analysis in addition to those acknowledged by the Evidence Review Committee that raise questions about its utility in reliably informing guideline recommendations.First, it was not prospectively planned to minimize potential bias.Second, it was based on study-level data, thereby precluding a deeper exploration into possible heterogeneity of treatment effect across key subgroups such as diabetes mellitus, chronic kidney disease, or age >60 years.Third, it was not adjusted for multiplicity to avoid spurious (falsepositive) conclusions.Fourth, the meta-analytic P values of 0.012 for stroke reduction and 0.033 for major adverse cardiovascular event reduction are not consistent with strong evidence against the null.For example, the P value of 0.033 for major
Abstract 12369: Dietary Salt Intake is Associated With Atrial Fibrillation
Authors: Olavi Ukkola, Tero Pääkkö, Marja-Leena Silaste, Heikki V Huikuri, Antero Kesaniemi
Journal: Circulation (2017)

The association of dietary salt and hypertension has been well documented. Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and, due to ageing of the population, its prevalence is ...
Predictive factors of pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids
Authors: Julia Herrou, Victoire De Lastours
Journal: Annals of the Rheumatic Diseases (2018)

We read with interest the article by Jun Won Park et al , describing in a retrospective study the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) to prevent Pneumocystis jiroveci pneumonia (PCP) in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids.1 High-dose glucocorticoid is indeed a well-known and major risk factor for PCP supporting the investigation carried out here. The conclusions of the work are that TMP-SMX prophylaxis is very effective and safe at preventing PCP.2 …
CDC20 regulates cardiac hypertrophy via targeting LC3-dependent autophagy
Authors: Yun-Peng Xie, Song Lai, Qiu-Yue Lin, Xin Xie, Jia-Wei Liao, Hong-Xia Wang, Cui Tian, Hui-Hua Li
Journal: Theranostics (2018)

Rationale: Sustained cardiac hypertrophy often leads to heart failure (HF).Understanding the regulation of cardiomyocyte growth is crucial for the treatment of adverse ventricular remodeling and HF.Cell division cycle 20 (CDC20) is an anaphase-promoting complex activator that is essential for cell division and tumorigenesis, but the role of CDC20 in cardiac hypertrophy is unknown.We aimed to test whether CDC20 participates in the regulation of pathological cardiac hypertrophy and investigate the underlying mechanism in vitro and in vivo.Methods: Male C57BL/6 mice were administered a recombinant adeno-associated virus serotype 9 (rAAV9) vector expressing CDC20 or a siRNA targeting CDC20 and their respective controls by tail intravenous injection.Results: Microarray analysis showed that CDC20 was significantly upregulated in the heart after angiotensin II infusion.Knockdown of CDC20 in cardiomyocytes and in the heart reduced cardiac hypertrophy upon agonist stimulation or transverse aortic constriction (TAC).Conversely, enforced expression of CDC20 in cardiomyocytes and in the heart aggravated the hypertrophic response.Furthermore, we found that CDC20 directly targeted LC3, a key regulator of autophagy, and promoted LC3 ubiquitination and degradation by the proteasome, which inhibited autophagy leading to hypertrophy.Moreover, knockdown of LC3 or inhibition of autophagy attenuated Ang II-induced cardiomyocyte hypertrophy after deletion of CDC20 in vitro.Conclusions: Our study reveals a novel cardiac hypertrophy regulatory mechanism that involves CDC20, LC3 and autophagy, and suggests that CDC20 could be a new therapeutic target for patients with hypertrophic heart diseases.
"Everything that is not curative is now palliative": A nurse perspective.
Authors: Hilde M. Buiting, Femke Botman, Veerle Busink, Elzbeth Oomen, Vincent K.Y. Ho
Journal: Journal of Clinical Oncology (2018)

127 Background: Advances in oncology increasingly result in protracted disease trajectories for patients with incurable cancer. This phase can be described as advanced / metastatic cancer and in which anti-cancer treatment should control symptoms, slow disease progression, and/or prolong life. It poses new challenges for patients and their doctors; it is unknown how and which disease labels are used by nurses. Methods: Qualitative ethnographic study, based on in-depth interviews with 13 oncology nurses at the day-care unit in a Dutch comprehensive cancer hospital. Results: A substantial number of nurses reported not to know whether patients were treated with a curative or palliative intent, and to follow a patient-centred approach. Other nurses clearly demarcated palliative patients, and some distinguished "real palliative patients" from patients with long-standing incurable cancer. When nurses were explicitly asked about medical terminology, many nurses were not very positive about the term "palliative". They considered this to be an old term, e.g. "Now everything that is not curative is palliative". Moreover, the term "palliative" could have an ambiguous/threatening meaning, especially for patients. Whereas nurses often associated the term "palliative" with alleviating symptoms, for patients this term was frequently associated with the approaching death. Most nurses therefore preferred not to use the term "palliative" in front of the patient; but only amongst nurses themselves. Since nurses had not previously been provoked to think about other terms, they were unsure whether "chronic" was the right term. Some indicated that cancer was rather different compared to other chronic diseases, others felt unsure when to use the term "chronic" at all. Conclusions: According to nurses, the use of specific medical terms such as "chronic" to describe the situation of patients in protracted disease trajectories is unclear. Although they acknowledge differences across the palliative care continuum, they refrain from using the word "palliative" in front of the patient. Nurses’ awareness of the disease stage (curative/palliative/ "chronic") might be important to optimise to patients’ specific needs in every disease phase.