tbuckley/cabot-search huggingface dataset:
Efficient Targeting and Activation of Antigen-Presenting Cells In Vivo after Modified mRNA Vaccine Administration in Rhesus Macaques
Authors: Frank Liang, Gustaf Lindgren, Ang Lin, Elizabeth A. Thompson, Sebastian Ols, Josefine Röhss, Shinu John, Kimberly Hassett, Olga Yuzhakov, Kapil Bahl, Luis A. Brito, Hugh Salter, Giuseppe Ciaramella, Karin Loré
Journal: Molecular Therapy (2017)

mRNA vaccines are rapidly emerging as a powerful platform for infectious diseases because they are well tolerated, immunogenic, and scalable and are built on precise but adaptable antigen design. We show that two immunizations of modified non-replicating mRNA encoding influenza H10 hemagglutinin (HA) and encapsulated in lipid nanoparticles (LNP) induce protective HA inhibition titers and H10-specific CD4+ T cell responses after intramuscular or intradermal delivery in rhesus macaques. Administration of LNP/mRNA induced rapid and local infiltration of neutrophils, monocytes, and dendritic cells (DCs) to the site of administration and the draining lymph nodes (LNs). While these cells efficiently internalized LNP, mainly monocytes and DCs translated the mRNA and upregulated key co-stimulatory receptors (CD80 and CD86). This coincided with upregulation of type I IFN-inducible genes, including MX1 and CXCL10. The innate immune activation was transient and resulted in priming of H10-specific CD4+ T cells exclusively in the vaccine-draining LNs. Collectively, this demonstrates that mRNA-based vaccines induce type-I IFN-polarized innate immunity and, when combined with antigen production by antigen-presenting cells, lead to generation of potent vaccine-specific responses.
PCSK9 Inhibitors, Statins, Low-Density Lipoprotein Cholesterol, Mevalonate Pathway, and Toxicity
Authors: Carlos Guijarro
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis
Authors: Pallavi Chaturvedi, Daniele M. Gilkes, Carmen Chak Lui Wong, Kshitiz Kshitiz, Weibo Luo, Huafeng Zhang, Hong Wei, Naoharu Takano, Luana Schito, Andre Levchenko, Gregg L. Semenza
Journal: Journal of Clinical Investigation (2013)
Using Data to Enhance Performance and Improve Quality and Safety in Surgery
Authors: Mitchell G. Goldenberg, James Jung, Teodor P. Grantcharov
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Overdiagnosis, ethics, and trolley problems: why factors other than outcomes matter—an essay by Stacy Carter
Authors: Stacy M Carter
Journal: BMJ (2017)

If the only ethically important consideration was the balance of benefit to harm, overdiagnosis might be less contested, writes <b>Stacy Carter</b>. But evidence and intuitions from famous thought experiments could explain some peoples' willingness to accept the harms of overdiagnosis—other factors may feel more important to them
Association of State Access Standards With Accessibility to Specialists for Medicaid Managed Care Enrollees
Authors: Chima D. Ndumele, Michael S. Cohen, Paul D. Cleary
Journal: JAMA Internal Medicine (2017)

Medicaid recipients have consistently reported less timely access to specialists than patients with other types of coverage. By 2018, state Medicaid agencies will be required by the Center for Medicare and Medicaid Services (CMS) to enact time and distance standards for managed care organizations to ensure an adequate supply of specialist physicians for enrollees; however, there have been no published studies of whether these policies have significant effects on access to specialty care.
<i>BJSM</i>educational editorials: methods matter
Authors: Evert Verhagen, Steven D Stovitz, Mohammad Ali Mansournia, Rasmus Oestergaard Nielsen, Ian Shrier
Journal: British Journal of Sports Medicine (2017)

Advancing the quality of research in the field of sports medicine is a BJSM aim. Therefore, BJSM publishes papers with a methodological focus, helping readers to better understand and interpret study outcomes (eg, refs 1–3). This has assisted our community translate study outcomes into practice. To further advance the field, the BJSM will publish a series of editorials addressing specific issues in research methodology that impact the conduct, presentation and interpretation of studies. Authorship is open, so please see this as a call for your submissions too.

The state of the art in research methods is continuously evolving and methodological papers advance the field of epidemiology and biostatistics. Just as our community adapts to advances in physiotherapy, imaging and sports science, we must embrace statistical method advances to ensure that shared decisions with athletes are based on accurate information.

If a publication claims that an intervention …
Oncology phase II clinical trials in 2011: Summary description and comparison to phase II trials in other subspecialties.
Authors: Yee Hong Chia
Journal: Journal of Clinical Oncology (2013)

e17568 Background: Phase II clinical trials in oncology have previously been reported to differ significantly in design compared to trials in other subspecialties. The purpose of this study is to provide a summary description of Phase II oncology clinical trials published in 2011, and to identify persistent major cross-specialty differences in clinical trial design. Methods: Records identified through a computerized literature search on PUBMED were reviewed manually using pre-defined criteria to identify abstracts of Phase II clinical trials published in 2011. The abstracts were classified according to variables including subspecialty, use of control group (active and/or placebo), randomization, blinding, and study conclusions. Trials with positive outcomes were defined as those in which the conclusion indicated that the intervention was safe and effective/worthy of further investigation. Statistical analysis was performed using the chi-squared test. Results: A total of 1,500 abstracts of Phase II clinical trials were identified, of which the majority (75%) describe trials on interventions for neoplastic diseases. Among oncology trials, the largest proportion of abstracts described trials evaluating intervention for hematologic neoplasms (16%), followed by upper and lower gastrointestinal (15%), lung (13%) and breast (11%) cancers. Compared to trials in other subspecialties, oncology trials are significantly less likely to include the use of randomization (17% vs 66%, p &lt; 0.0001), blinding (3% vs 44%, p &lt; 0.0001), and control (13% vs 70%, p &lt; 0.0001). The majority of the abstracts reported positive outcomes (66% for oncology; 74% for the other subspecialties). Among oncology trials, trials utilizing a control group are less likely to report positive outcomes than those without a control group (53% vs 67%, p = 0.002). Conclusions: Major differences in design still exist between Phase II trials in oncology and other subspecialties. Only a minority of oncology trials report the use of randomization, blinding, or control groups. Whether the growing interest in randomized Phase II oncology trials will translate into a larger proportion of such trials in the future remains to be seen.
Pharmacokinetics and bioavailability of a novel microgranular curcumin formulation in healthy volunteers versus head and neck cancer patients.
Authors: Tara Moore-Medlin, Brian Latimer, Oleksandr Ekshyyan, Kenneth McMartin, Tammy Dugas, Xiaohui Ma, Neil Nathan, Hunter Christy, Gloria Caldito, Cherie-Ann Nathan
Journal: Journal of Clinical Oncology (2015)

e12576 Background: Curcumin has been widely recognized as a natural agent with various anti-cancer properties. Limitations include its poor bioavailability and large bulky standard capsular formulations for head and neck squamous cell carcinoma (HNSCC) patients. We wanted to compare serum levels of a novel microgranular curcumin formulation administered transmucosally in healthy volunteers (HV) to HNSCC patients after a one time dose. Methods: Under IRB approval, HV (n = 8) and HNSCC patients (n = 17) self-administered 4g of microgranular curcumin. Two HV and five HNSCC patients were African-American. Blood was collected and processed at baseline, 15 min, 30 min, 1 h, 2 h and 4 h post dosing. Serum was analyzed for the presence of curcumin by High Performance Liquid Chromatography (HPLC). Results: Microgranular curcumin was consumed easily and was well tolerated by all subjects. A wide range of serum curcumin concentrations was observed (9.77-711.3 ng/ml). By using microgranular curcumin administered transmucosally we achieved much higher levels of curcumin in serum compared to trials using standard capsules (historical controls). HV had significantly higher curcumin levels than HNSCC patients at all timepoints (p < 0.05). African-Americans had significantly higher curcumin levels than Caucasians in both cohorts (HV: at 1h; p = 0.046; and 2h; p = 0.046; HNSCC patients: at 15 min; p = 0.09; and at 2h; p = 0.09). Conclusions: Transmucosal administration of microgranular curcumin was well-tolerated in both study cohorts and resulted in improved bioavailability compared to trials that used capsular formulation. Significantly higher serum curcumin levels were observed at various timepoints in HV compared to HNSCC patients and in African-Americans compared to Caucasians. Further investigations in large study groups are needed to confirm this finding. The higher levels noted in HV are particularly exciting as curcumin is more likely to be beneficial in prevention of cancer in smokers and tobacco users at risk for oral cancer. Clinical trial information: NCT01160302.
Impact of Notch disruption on myeloid development
Authors: O L Francis, K K Chaudhry, T Lamprecht, J M Klco
Journal: Blood Cancer Journal (2017)

The Notch pathway is a conserved signaling network that regulates many cellular processes including renewal of stem cells, differentiation of multiple cell lineages, proliferation and apoptosis.1 Notch signaling involves the binding of Notch ligands to Notch receptors followed by proteolytic cleavage events, translocation of intracellular Notch (ICN) to the nucleus and regulation of target genes via the interaction of transcription factor CSL/RBPJ and the MAML family of transcriptional co-activators.1, 2 The Notch pathway is involved in lymphoid development and recurrent activating mutations in NOTCH1 contribute to T lymphoblastic leukemias.3 Whether Notch signaling is actively involved in the regulation of myeloid development and myeloid leukemogenesis is less clear due to conflicting reports.4, 5, 6 In this study, we abrogated canonical Notch signaling throughout the hematopoietic system to evaluate the role of Notch in myelopoiesis and to conclusively determine if inhibition of Notch signaling can contribute to aberrant myelopoiesis and lead to the development of a myeloid neoplasm.
Issues with European guidelines for phenylketonuria – Authors' reply
Authors: Francjan J van Spronsen, Annemiek M J van Wegberg, Kirsten Ahring, Amaya Bélanger-Quintana, Nenad Blau, Annet M Bosch, Alberto Burlina, Jaime Campistol, Francois Feillet, Maria Giżewska, Stephan C Huijbregts, Shauna Kearney, Vincenzo Leuzzi, Francois Maillot, Ania C Muntau, Fritz K Trefz, Margreet van Rijn, Anita MacDonald
Journal: The Lancet Diabetes & Endocrinology (2017)
Topography of Prostate Cancer Recurrence After Radiation Therapy: A Detailed Mapping Study of Salvage Radical Prostatectomy Specimens
Authors: Toshikazu Takeda, Amy L Tin, Renato B Corradi, Maha Mamoor, Nicole E Benfante, Daniel D Sjoberg, Peter T Scardino, James A Eastham, Samson W Fine, Karim A Touijer
Journal: European Urology (2017)
National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer
Authors: Christopher P. Childers, Kimberly K. Childers, Melinda Maggard-Gibbons, James Macinko
Journal: Journal of Clinical Oncology (2017)

Purpose In the United States, 3.8 million women have a history of breast (BC) or ovarian cancer (OC). Up to 15% of cases are attributable to heritable mutations, which, if identified, provide critical knowledge for treatment and preventive care. It is unknown how many patients who are at high risk for these mutations have not been tested and how rates vary by risk criteria. Methods We used pooled cross-sectional data from three Cancer Control Modules (2005, 2010, 2015) of the National Health Interview Survey, a national in-person household interview survey. Eligible patients were adult females with a history of BC and/or OC meeting select 2017 National Comprehensive Cancer Network eligibility criteria on the basis of age of diagnosis and family history. Outcomes included the proportion of individuals reporting a history of discussing genetic testing with a health professional, being advised to undergo genetic testing, or undergoing genetic testing for BC or OC. Results Of 47,218 women, 2.7% had a BC history and 0.4% had an OC history. For BC, 35.6% met one or more select eligibility criteria; of those, 29.0% discussed, 20.2% were advised to undergo, and 15.3% underwent genetic testing. Testing rates for individual eligibility criteria ranged from 6.2% (relative with OC) to 18.2% (diagnosis ≤ 45 years of age). For OC, 15.1% discussed, 13.1% were advised to undergo, and 10.5% underwent testing. Using only four BC eligibility criteria and all patients with OC, an estimated 1.2 to 1.3 million individuals failed to receive testing. Conclusion Fewer than one in five individuals with a history of BC or OC meeting select National Cancer Comprehensive Network criteria have undergone genetic testing. Most have never discussed testing with a health care provider. Large national efforts are warranted to address this unmet need.
Effect of CA125/MUC16 on complement-dependent cytotoxicity (CDC) of farletuzumab and other CDC-mediating antibodies via inhibition of antibody-C1q binding.
Authors: J Bradford Kline, Shawn Fernando, Stephen Harley, Luigi Grasso, Nicholas C Nicolaides
Journal: Journal of Clinical Oncology (2017)

e23082 Background: Human cancers employ a number of mechanisms to evade host immune responses. Here we report the effects of the tumor-shed antigen CA125 on suppressing complement-dependent cellular cytotoxicity (CDC). This finding relates to a prespecified subgroup analysis of an 1100 patient Ph3 clinical trial testing the investigational agent farletuzumab, a monoclonal antibody (mAb) to folate receptor alpha, plus standard-of-care chemotherapy in patients with recurrent ovarian cancer. In this study, patients with low levels of CA125 (no greater than 3X the upper limit of normal) treated with farletuzumab compared to placebo demonstrated improvements in both progression free survival (HR 0.49, p = 0.0028) and overall survival (HR 0.44, p = 0.0108). Farletuzumab’s pharmacologic activity is mediated in part through antibody dependent cellular cytotoxicity (ADCC) and CDC. Here we show that CA125 inhibits IgG1- and IgM-mediated CDC by suppressing antibody interaction with the C1q complement-initiating protein. Methods: Functional assays employing cell lines expressing antibody-specific antigens were used to measure CDC activity. CA125 isolates from various patients and cell lines were used to monitor CA125 effects on complement function. ELISA assays were used to measure the effects of CA125 inhibition on C1q-antibody interaction. Results: Functional assays showed that CA125 suppressed antibody-mediated CDC in a dose dependent fashion. Molecular studies revealed that this suppression is caused by CA125 binding to antibody, leading to suppression of antibody-C1q interaction. Conclusions: Here we demonstrate that CA125 can elicit immunosuppression by perturbing the interaction of tumor targeting antibodies and the C1q complement-initiating protein. This effect is through a direct binding of CA125 to antibody. These findings provide new insights into the potential biological mechanisms by which tumors produce tumor shed antigens like CA125 to suppress host immune responses such as CDC. This finding has important clinical applications for the development of therapeutics utilizing complement-mediated mechanisms.
Serum ghrelin is associated with risk of colorectal adenocarcinomas in the ATBC study
Authors: Gwen Murphy, Amanda J Cross, Sanford M Dawsey, Frank Z Stanczyk, Farin Kamangar, Stephanie J Weinstein, Philip R Taylor, Satu Männistö, Demetrius Albanes, Christian C Abnet, Neal D Freedman
Journal: Gut (2017)

Background Colorectal cancers are the third most common cancers in women and men in the USA. While dietary and lifestyle factors such as Western diet, physical inactivity and obesity have been linked to an increased risk of this malignancy, the mechanisms for these associations are unclear. GI hormones, including ghrelin, are involved in energy balance by mediating appetite and metabolism; however, the association between ghrelin and colorectal cancer has not been studied. Methods We conducted a case–control study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish smokers (aged 50–69 years) to examine serum ghrelin concentration and colorectal cancer risk. Data from 284 colon and 239 rectal cancers and 523 controls (matched on age, date of blood draw and serum availability) were analysed. ORs and 95% CIs were calculated using multivariable (conditional) logistic regression. Results Overall, low-serum ghrelin was significantly associated with increased risk of colorectal cancer (Q1 vs Q4: OR:1.57, 95% CI 1.05 to 2.34). For individuals developing tumours within 10 years of blood draw, those in the lowest quartile of serum ghrelin concentrations were statistically significantly more likely to develop colorectal cancers than those with higher serum ghrelin concentrations (OR: 10.86, 95% CI 5.01 to 23.55). However, for individuals with tumours developing more than 20 years after blood draw, low-serum ghrelin concentrations were associated with a decreased risk of colorectal cancer relative to those with the highest serum ghrelin concentrations (OR: 0.26, 95% CI 0.11 to 0.64). Conclusion Low-serum ghrelin was associated with an increased colorectal cancer risk within 10 years of blood draw with a decreased risk for developing colorectal cancer more than 20 years after blood draw. These results suggest that ghrelin concentrations may vary across the carcinogenic process.
AB1197-HPR Validity and reliability of a smartphone goniometer application for measuring hip range of motion in patients with hip osteoarthritis: a pilot study
Authors: DC Sarac, G Yalcinkaya, B Unver
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoarthritis (OA) of the hip affects the entire joint structure and function and leads joint capsular changes which result limitation in range of motion (ROM). Therefore, measuring ROM is an essential part of the hip assessment. Various measurement tools are available for determining the ROM such as universal goniometers (UG), digital inclinometers, motion analysis systems. Recently, smartphones equipped with suitable applications are able to measure ROM. <h3>Objectives</h3> The aim of this study was to determine the inter-rater and intra-rater reliability of a smartphone application "PT Goniometer<sup>©</sup> 2015 Mark Busman" (PTG) and investigate the agreement within PTG versus UG for active hip ROMs in patients with hip OA. <h3>Methods</h3> This study included eight people who were diagnosed with hip OA. Two physiotherapists performed the ROM measurements on affected hips by using PTG and UG. UG was employed as the reference standard. Hip ROM tests were performed in the following order; flexion, abduction, internal and external rotation. Intraclass correlation coefficient (ICC) models were used to determine the intra-rater and inter-rater reliability. The Spearman correlation coefficients were used to establish validity of PTG. <h3>Results</h3> The PTG smartphone application demonstrated good to excellent inter-rater and intra-rater reliability (ICCs &gt;0.75) for all measured hip movements in patients with hip OA. ICC scores, minimum detectable change (MDC<sub>95</sub>) and standart error of measurement (SEM) values were indicated in Table 1 and Table 2. Additionally,UG and PTG application methods demonstrated positive correlations for all hip movements (p&lt;0.05). <h3>Conclusions</h3> High correlations obtained in this pilot study suggest that using a smartphone application might be a valid and a reliable method for measuring hip ROM in patients with hip OA and smartphone applications can be used in clinical settings. Studies with larger population are required for further investigation of smartphones9 psychometric properties on measuring hip ROM. <h3>Disclosure of Interest</h3> None declared
脂質代謝:代替的に活性化されたマクロファージはカテコールアミンを合成せず,脂肪組織の適応熱産生に寄与していない
Authors: Fischer Katrin, Finan Brian, Clemmensen Christoffer, Glasmacher Elke, Keipert Susanne, Jastroch Martin, Collden Gustav, Tschoep Matthias H, Mueller Timo D, Ruiz Henry H, Jhun Kevin, Oberlin Douglas J, Van Der Heide Verena, Shin Andrew C, Homann Dirk, Buettner Christoph, Kalinovich Anastasia, Petrovic Natasa, Nedergaard Jan, Cannon Barbara, Wolf Yochai, Jung Steffen, Divanovic Senad, Brombacher Frank, Nagler Joachim, Schramm Karl‐Werner, Medrikova Dasa, Herzig Stephan, Woods Stephen C
Journal: Nature Medicine (2017)