tbuckley/cabot-search huggingface dataset:
Annals Story Slam - Escape From Iraq: A Refugee Family's Story of Resilience and Hope
Authors: Kimberly Carter
Journal: Annals of Internal Medicine (2018)

Web Exclusives3 April 2018Annals Story Slam - Escape From Iraq: A Refugee Family's Story of Resilience and HopeFREEKimberly Carter, PharmDKimberly Carter, PharmDThomas Jefferson University, Philadelphia, Pennsylvania (K.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0006 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Escape From Iraq: A Refugee Family's Story of Resilience and Hope "Escape From Iraq: A Refugee Family's Story of Resilience and Hope," by Dr. Kimberly Carter (Duration 5:51)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (K.C.)Corresponding Author: Kimberly Carter, PharmD; e-mail, kimberly.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 April 2018Volume 168, Issue 7Page: SS1 ePublished: 3 April 2018 Issue Published: 3 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications
Authors: Wei Wu, Li Luo, Yi Wang, Qi Wu, Han-Bin Dai, Jian-Shu Li, Colm Durkan, Nan Wang, Gui-Xue Wang
Journal: Theranostics (2018)

Nanotechnology-based antitumor drug delivery systems, known as nanocarriers, have demonstrated their efficacy in recent years. Typically, the size of the nanocarriers is around 100 nm. It is imperative to achieve an optimum size of these nanocarriers which must be designed uniquely for each type of delivery process. For pH-responsive nanocarriers with programmable size, changes in pH (~6.5 for tumor tissue, ~5.5 for endosomes, and ~5.0 for lysosomes) may serve as an endogenous stimulus improving the safety and therapeutic efficacy of antitumor drugs. This review focuses on current advanced pH-responsive nanocarriers with programmable size changes for anticancer drug delivery. In particular, pH-responsive mechanisms for nanocarrier retention at tumor sites, size reduction for penetrating into tumor parenchyma, escaping from endo/lysosomes, and swelling or disassembly for drug release will be highlighted. Additional trends and challenges of employing these nanocarriers in future clinical applications are also addressed.
Commissioners are warned not to spend too little on mental health
Authors: Adrian O’Dowd
Journal: BMJ (2018)

Commissioners have been told to improve spending on mental health services locally or face sanctions from NHS England.

A letter was sent on 4 April by NHS England’s national mental health director, Claire Murdoch, to all clinical commissioning groups and sustainability and transformation partnership leads.

The letter follows up the Refreshing NHS Plans for 2018-19 guidance issued in February,1 which emphasised that CCGs must meet the Mental Health Investment Standard, meaning that their 2018-19 investment in mental health services …
Human adipose mesenchymal stem cells overexpressing dual chemotactic gene showed enhanced angiogenic capacity in ischaemic hindlimb model
Authors: Younggeul Min, Seongho Han, Hyun Aae Ryu, Sung-Whan Kim
Journal: Cardiovascular Research (2018)

In present study, we sought to characterize the angio-vasculogenic property of human adipose mesenchymal stem cells (ASCs) overexpressing dual chemokine GCP-2 and SDF-1α (ASC-G/S) and to determine the therapeutic potential of ASC-G/S in the context of experimental ischaemia. We generated ASC-G/S line and performed flow cytometry, quantitative (q)-PCR, Matrigel tube formation, Matrigel plug assays, and in vivo therapeutic assays using hind limb ischaemia mouse model. Q-PCR results showed that the representative pro-angiogenic factors were highly upregulated in ASC-G/S compared with ASCs single chemokine overexpressing GCP-2 (ASC-G). In addition, ASC-G/S exhibited high expression of endothelium-specific genes shch as vWF and Flk-1 and showed robust in vitro micro-vascular formation. ASC-G/S was transplanted into ischaemic mouse hind limbs and compared with control groups. ASC-G/S injection prevented limb loss and augmented blood perfusion, suggesting that ASC-G/S enhances neovascularization in hind limb ischaemia. In addition, transplanted ASC-G/S revealed high vasculogenic potential in vivo compared with transplanted ASC-G. Our data suggest that ASC-G/S has high therapeutic effects on hind limb ischaemia via robust angiogenic and vasculogenic action.
Acute Coronary Syndrome in a 44-Year-Old Woman
Authors: Francisco Aguilar, Deepika Kalisetti, Sanjog Kalra
Journal: JAMA Cardiology (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 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
Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet
Authors: Elena Loche, Heather L Blackmore, Asha A Carpenter, Jessica H Beeson, Adele Pinnock, Thomas J Ashmore, Catherine E Aiken, Juliana de Almeida-Faria, Josca M Schoonejans, Dino A Giussani, Denise S Fernandez-Twinn, Susan E Ozanne
Journal: Cardiovascular Research (2018)

Obesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac structure and function using an established mouse model of maternal diet-induced obesity.The impact of the maternal and postnatal environment on the offspring metabolic profile, arterial blood pressure, cardiac structure, and function was assessed in 8-week-old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the transcriptional re-activation of cardiac fetal genes as well as genes involved in the regulation of contractile function and matrix remodelling in the adult heart were determined as potential mediators of effects on cardiac function. In the adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal obesity increased serum insulin (P < 0.0001) and leptin levels (P < 0.0001); maternal obesity (P = 0.001) and a post-weaning obesogenic diet (P = 0.002) increased absolute heart weight; maternal obesity (P = 0.01) and offspring obesity (P = 0.01) caused cardiac dysfunction but effects were not additive; cardiac dysfunction resulting from maternal obesity was associated with re-expression of cardiac fetal genes (Myh7: Myh6 ratio; P = 0.0004), however, these genes were not affected by offspring diet; maternal obesity (P = 0.02); and offspring obesity (P = 0.05) caused hypertension and effects were additive.Maternal diet-induced obesity and offspring obesity independently promote cardiac dysfunction and hypertension in adult male progeny. Exposure to maternal obesity alone programmed cardiac dysfunction, associated with hallmarks of pathological left ventricular hypertrophy, including increased cardiomyocyte area, upregulation of fetal genes, and remodelling of cardiac structure. These data highlight that the perinatal period is just as important as adult-onset obesity in predicting CVD risk. Therefore, early developmental periods are key intervention windows to reduce the prevalence of CVD.
Preprints: An underutilized mechanism to accelerate outbreak science
Authors: Michael A. Johansson, Nicholas G. Reich, Lauren Ancel Meyers, Marc Lipsitch
Journal: PLoS Medicine (2018)

Preprints-manuscripts posted openly online prior to peer review-offer an opportunity to accelerate the dissemination of scientific findings to support responses to infectious disease outbreaks.• Preprints posted during the Ebola and Zika outbreaks included novel analyses
Device-Related Thrombosis After Percutaneous Left Atrial Appendage Occlusion for Atrial Fibrillation
Authors: Laurent Fauchier, Alexandre Cinaud, François Brigadeau, Antoine Lepillier, Bertrand Pierre, Selim Abbey, Marjaneh Fatemi, Frederic Franceschi, Paul Guedeney, Peggy Jacon, Olivier Paziaud, Sandrine Venier, Jean Claude Deharo, Daniel Gras, Didier Klug, Jacques Mansourati, Gilles Montalescot, Olivier Piot, Pascal Defaye
Journal: Journal of the American College of Cardiology (2018)
A precision medicine strategy to identify the FGFR pathway as a novel target in colorectal cancer liver metastasis.
Authors: Erdem Altunel, Jason Somarelli, So Young Kim, Wayne Glover, Gabrielle Rupprecht, Shiaowen David Hsu
Journal: Journal of Clinical Oncology (2018)

660 Background: Colorectal cancer liver metastasis (CRCLM) continues to be a major health problem and despite extensive efforts to develop new drugs, median survival remains at a mere 30 months. The purpose of our study is 1. Develop a precision medicine strategy for patients with CRCLM and 2. Discover novel pathways and treatments to improve outcomes. Methods: In order to develop a precision medicine strategy, 6 matched patient derived xenografts (PDX) and cell lines were established from patients undergoing resection of their CRCLM. A high-throughput drug screen containing over 100 FDA approved drugs was first used in vitro on 3 cell lines to identify therapeutic targets. The top therapeutic targets were validated in vivo. RNA seq was then performed to identify potential predictive markers of response. Results: Our high-throughput drug screen performed on 3 early passage CRC cell lines (CRC057, CRC119 and CRC240) identified ponatinib, a multi TKI, as the only agent to inhibit all 3 cell lines. Subsequent growth inhibition analysis identified the fibroblast growth factor receptor (FGFR) as the main target of ponatinib. In vitro findings were confirmed in vivo in matched PDXs. Western blot analysis post treatment showed evidence of decreased phospho-FGFRs. Further analysis of the main downstream signaling pathways of FGFR (RAS/PI3K/AKT, RAS/MEK/ERK and STAT) demonstrated that the STAT pathway was effectively targeted in all 3 cell lines. In contrast, the ERK pathway was targeted in CRC240 and CRC057 while the p-AKT was targeted in CRC119. Finally, RNAseq revealed different isoforms and mutations in these samples. Conclusions: We have developed a precision medicine strategy for patients with CRCLM using matched cell lines and PDXs coupled with high throughput drug screens and genomic analysis to identify novel targets and specifically identified the FGFR/STAT axis as a therapeutic target. Furthermore, co-targeting FGFR and its downstream pathways may provide synergy and lead to combinatorial therapies that can improve patient outcomes. Finally, RNAseq data can be used to develop predictive markers of therapy.
First-in-Human Phase I Study of AC0010, a Mutant-Selective EGFR Inhibitor in Non–Small Cell Lung Cancer: Safety, Efficacy, and Potential Mechanism of Resistance
Authors: Yuxiang Ma, Xin Zheng, Hongyun Zhao, Wenfeng Fang, Yang Zhang, Jieying Ge, Lu Wang, Weicong Wang, Ji Jiang, Shaokun Chuai, Zhou Zhang, Wanhong Xu, Xiao Xu, Pei Hu, Li Zhang
Journal: Journal of Thoracic Oncology (2018)
A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration
Authors: Amir H. Kashani, Jane S. Lebkowski, Firas M. Rahhal, Robert L. Avery, Hani Salehi-Had, Wei Dang, Chih-Min Lin, Debbie Mitra, Danhong Zhu, Biju B. Thomas, Sherry T. Hikita, Britney O. Pennington, Lincoln V. Johnson, Dennis O. Clegg, David R. Hinton, Mark S. Humayun
Journal: Science Translational Medicine (2018)

Implantation of a human embryonic stem cell–derived retinal pigment epithelial monolayer is feasible in human subjects with advanced, dry age-related macular degeneration.
Complexity and possession: Gender and social structure in the variability of shamanic traits
Authors: Connor P. Wood, Kate J. Stockly
Journal: Behavioral and Brain Sciences (2018)

Abstract Singh deploys cultural evolution to explain recurrent features of shamanistic trance forms, but fails to substantively address important distinctions between these forms. Possession trance (vs. trance without possession) is disproportionately female-dominated and found in complex societies. The effects of cultural conditions on shamanism thus extend beyond its presence or absence and are vital for modeling its professionalization and spread.
Diversity Beyond Race and Ethnicity: Enhancing Inclusion With an Expanded Definition of Diversity
Authors: Gwendolyn P. Quinn, Clement K. Gwede, Cathy D. Meade
Journal: The American Journal of Bioethics (2018)

"Diversity Beyond Race and Ethnicity: Enhancing Inclusion With an Expanded Definition of Diversity." The American Journal of Bioethics, 18(4), pp. 47–48
Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance
Authors: Jonathan Edward Millar, Viktor von Bahr, Maximillian V Malfertheiner, Katrina K Ki, Meredith A Redd, Nicole Bartnikowski, Jacky Y Suen, Danny Francis McAuley, John F Fraser
Journal: Thorax (2018)

Mesenchymal stem cells (MSCs) have attracted attention as a potential therapy for Acute Respiratory Distress Syndrome (ARDS). At the same time, the use of extracorporeal membrane oxygenation (ECMO) has increased among patients with severe ARDS. To date, early clinical trials of MSCs in ARDS have excluded patients supported by ECMO. Here we provide evidence from an ex-vivo model of ECMO to suggest that the intravascular administration of MSCs during ECMO may adversely impact the function of a membrane oxygenator. The addition of clinical grade MSCs resulted in a reduction of flow through the circuit in comparison to controls (0.6 ±0.35 L min-1vs 4.12 ± 0.03 L min-1, at 240 minutes) and an increase in the transoygenator pressure gradient (101±9 mmHg vs 21±4 mmHg, at 240 minutes). Subsequent immunohistochemistry analysis demonstrated quantities of MSCs highly adherent to membrane oxygenator fibres. This study highlights the potential harm associated with MSC therapy during ECMO and suggests further areas of research required to advance the translation of cell therapy in this population.
Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population
Authors: Ashley C. Bradford, W. David Bradford, Amanda Abraham, Grace Bagwell Adams
Journal: JAMA Internal Medicine (2018)

Opioid-related mortality increased by 15.6% from 2014 to 2015 and increased almost 320% between 2000 and 2015. Recent research finds that the use of all pain medications (opioid and nonopioid collectively) decreases in Medicare Part D and Medicaid populations when states approve medical cannabis laws (MCLs). The association between MCLs and opioid prescriptions is not well understood.To examine the association between prescribing patterns for opioids in Medicare Part D and the implementation of state MCLs.Longitudinal analysis of the daily doses of opioids filled in Medicare Part D for all opioids as a group and for categories of opioids by state and state-level MCLs from 2010 through 2015. Separate models were estimated first for whether the state had implemented any MCL and second for whether a state had implemented either a dispensary-based or a home cultivation only-based MCL.The primary outcome measure was the total number of daily opioid doses prescribed (in millions) in each US state for all opioids. The secondary analysis examined the association between MCLs separately by opioid class.From 2010 to 2015 there were 23.08 million daily doses of any opioid dispensed per year in the average state under Medicare Part D. Multiple regression analysis results found that patients filled fewer daily doses of any opioid in states with an MCL. The associations between MCLs and any opioid prescribing were statistically significant when we took the type of MCL into account: states with active dispensaries saw 3.742 million fewer daily doses filled (95% CI, -6.289 to -1.194); states with home cultivation only MCLs saw 1.792 million fewer filled daily doses (95% CI, -3.532 to -0.052). Results varied by type of opioid, with statistically significant estimated negative associations observed for hydrocodone and morphine. Hydrocodone use decreased by 2.320 million daily doses (or 17.4%) filled with dispensary-based MCLs (95% CI, -3.782 to -0.859; P = .002) and decreased by 1.256 million daily doses (or 9.4%) filled with home-cultivation-only-based MCLs (95% CI, -2.319 to -0.193; P = .02). Morphine use decreased by 0.361 million daily doses (or 20.7%) filled with dispensary-based MCLs (95% CI, -0.718 to -0.005; P = .047).Medical cannabis laws are associated with significant reductions in opioid prescribing in the Medicare Part D population. This finding was particularly strong in states that permit dispensaries, and for reductions in hydrocodone and morphine prescriptions.
John Weston Smith
Authors: Paul Weston Smith
Journal: BMJ (2018)

John Weston Smith decided on a career in medicine despite coming from a family with no medical background or experience of higher education. His father was a wages clerk for the Midland Red Bus Company and his mother a housewife. John was encouraged in his choice by Margaret Sheldon, the family GP. He lived at home as a student.

After qualifying he worked as a registrar in obstetrics at Dudley Road Hospital in Birmingham, but then decided on a career in general practice. He worked as an assistant in a practice in Birmingham but also opened his own practice, with friends and family members as patients, on 5 July 1948, the first day of the NHS.

He struggled to find a partnership because he had been a conscientious objector on religious grounds during the war. He moved to a two handed practice in Tamworth, Staffordshire, in 1949, where he …
Role of Stress Kinase JNK in Binge Alcohol-Evoked Atrial Arrhythmia
Authors: Jiajie Yan, Justin K. Thomson, Weiwei Zhao, Xianlong Gao, Fei Huang, Biyi Chen, Qingrong Liang, Long-Sheng Song, Michael Fill, Xun Ai
Journal: Journal of the American College of Cardiology (2018)

Excessive binge alcohol drinking has acute cardiac arrhythmogenic effects, including promotion of atrial fibrillation (AF), which underlies "Holiday Heart Syndrome." The mechanism that couples binge alcohol abuse with AF susceptibility remains unclear. We previously reported stress-activated c-Jun N-terminal kinase (JNK) signaling contributes to AF development. This is interesting because JNK is implicated in alcohol-caused organ malfunction beyond the heart. The purpose of this study was to detail how JNK promotes binge alcohol-evoked susceptibility to AF. The authors found binge alcohol-exposure leads to activated JNK, specifically JNK2. Furthermore, binge alcohol induces AF, higher incidence of diastolic intracellular Ca2+ activity (Ca2+ waves, sarcoplasmic reticulum [SR] Ca2+ leakage), and membrane voltage (Vm) and systolic Ca2+ release spatiotemporal heterogeneity (ΔtVm-Ca). These changes were completely eliminated by JNK inhibition both in vivo and in vitro. Calmodulin kinase II (CaMKII) is a proarrhythmic molecule known to drive SR Ca2+ mishandling. The authors report for the first time that binge alcohol activates JNK2, which subsequently phosphorylates the CaMKII protein, enhancing CaMKII-driven SR Ca2+ mishandling. CaMKII inhibition eliminates binge alcohol-evoked arrhythmic activities. Our studies demonstrate that binge alcohol exposure activates JNK2 in atria, which then drives CaMKII activation, prompting aberrant Ca2+ waves and, thus, enhanced susceptibility to atrial arrhythmia. Our results reveal a previously unrecognized form of alcohol-driven kinase-on-kinase proarrhythmic crosstalk. Atrial JNK2 function represents a potential novel therapeutic target to treat and/or prevent AF.
Complete intracranial response to talimogene laherparepvec (T-Vec), pembrolizumab and whole brain radiotherapy in a patient with melanoma brain metastases refractory to dual checkpoint-inhibition
Authors: Zoë Blake, Douglas K. Marks, Robyn D. Gartrell, Thomas Hart, Patti Horton, Simon K. Cheng, Bret Taback, Basil A. Horst, Yvonne M. Saenger
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy. <h3>Case presentation</h3> We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases. This patient achieved a complete CNS response and partial systemic response with standard whole brain radiation therapy (WBRT) combined with Talimogene laherparepvec (T-Vec) and pembrolizumab. <h3>Conclusion</h3> Patients who do not respond to one immunotherapy combination may respond during treatment with an alternate combination, even in the presence of multiple brain metastases. Biomarkers are needed to assist clinicians in evidence based clinical decision making after progression on first line immunotherapy to determine whether response can be achieved with second line immunotherapy.