tbuckley/cabot-search huggingface dataset:
Ethics and the Legalization of Physician-Assisted Suicide
Authors: Banu E. Symington
Journal: Annals of Internal Medicine (2018)

Letters5 June 2018Ethics and the Legalization of Physician-Assisted SuicideBanu E. Symington, MDBanu E. Symington, MDSweetwater Regional Cancer Center, Memorial Hospital of Sweetwater County, Rock Springs, Wyoming (B.E.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0079 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As a longtime member of the ACP and a practicing oncologist, I was disappointed in Sulmasy and colleagues' (1) position paper on the important topic of assisted dying. My disappointment started with the nomenclature—that is, the choice of the highly emotionally charged term physician-assisted suicide (PAS), which plays on readers' emotions. Patients are requesting assistance in ending a chronic medical condition, and a better term would be assisted dying or PAD.My disappointment continued with the oversimplification involved in assuming that the desire for PAD is due to inadequate symptom control or inappropriate depression. This assumption is ...Reference1. Snyder L, Mueller PS; Ethics, Professionalism and Human Rights Committee of the American College of Physicians. Ethics and the legalization of physician-assisted suicide: an American College of Physicians position paper. Ann Intern Med. 2017;167:576-8. [PMID: 28975242] doi:10.7326/M17-0938 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Sweetwater Regional Cancer Center, Memorial Hospital of Sweetwater County, Rock Springs, Wyoming (B.E.S.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0079. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEthics and the Legalization of Physician-Assisted Suicide: An American College of Physicians Position Paper Lois Snyder Sulmasy , Paul S. Mueller , and Ethics and the Legalization of Physician-Assisted Suicide Christie Reimer Ethics and the Legalization of Physician-Assisted Suicide Allen H. Roberts II Ethics and the Legalization of Physician-Assisted Suicide Timothy L. Gieseke Ethics and the Legalization of Physician-Assisted Suicide Lois Snyder Sulmasy and Paul S. Mueller Ethics and the Legalization of Physician-Assisted Suicide E. Wesley Ely Metrics 5 June 2018Volume 168, Issue 11Page: 833-834KeywordsDisclosureDrug psychotherapyDrugsEmotionsFearMedical conditionsNauseaPalliative carePeriodic acid SchiffSuicide ePublished: 5 June 2018 Issue Published: 5 June 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Sub‐Micrometer Au@PDA‐<sup>125</sup>I Particles as Theranostic Embolism Beads for Radiosensitization and SPECT/CT Monitoring
Authors: Gaofeng Sun, Tao Wang, Xiao Li, Danni Li, Ye Peng, Xiaoke Wang, Guorong Jia, Weiwei Su, Chao Cheng, Jian Yang, Changjing Zuo
Journal: Advanced Healthcare Materials (2018)

Abstract Au nanoparticles (3.8 ± 0.6 nm) are assembled to sub‐micrometer Au particles (186.3 ± 20.4 nm) and covered with adhesive polydopamine (PDA) as embolism beads (198.8 ± 23.2 nm). Radioactive iodine‐125 is labeled to Au@PDA to introduce the function of intra‐irradiation. For the therapeutic effects of Au@PDA‐ 125 I, Au particles sensitize the radiation to MHCC97H hepatoma cells and tumor‐bearing mice. At the cellular level, after being treated with a relatively low‐dose (5 Gy) γ‐ray, Au‐sensitized radiotherapy (RT) leads to an immediate increase of intracellular reactive oxygen species, accompanying with an increase of cell apoptosis. Due to the intra‐irradiation, self‐healing of RT‐leaded DNA double‐strand breakage is suppressed, inducing a further increase of cell apoptosis after RT treatment. Likewise, 3 cycles of sensitized RT leads to a valid control of tumor volume growth, but Au@PDA‐ 125 I has no harm or radioactive residual on or in the radiosensitive organs, including the thyroid, heart, lungs, liver, and spleen. Additionally, photons emitted from 125 I and high X‐ray absorption of the Au element makes the beads suitable for single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Therefore, as theranostic embolism beads, Au@PDA‐ 125 I can both enhance the therapeutic effects of external RT, and provide a real‐time SPECT/CT monitoring of therapeutic time window.
Acute and chronic neurological consequences of early-life Zika virus infection in mice
Authors: Isis Nem de Oliveira Souza, Paula S. Frost, Julia V. França, Jéssica B. Nascimento-Viana, Rômulo L. S. Neris, Leandro Freitas, Daniel J. L. L. Pinheiro, Clara O. Nogueira, Gilda Neves, Leila Chimelli, Fernanda G. De Felice, Ésper A. Cavalheiro, Sergio T. Ferreira, Iranaia Assunção-Miranda, Claudia P. Figueiredo, Andrea T. Da Poian, Julia R. Clarke
Journal: Science Translational Medicine (2018)

Infection by Zika virus triggers epileptic seizures in newborn mice and leads to viral persistence in the brain and behavioral deficits in adulthood.
Fertility preservation use and outcomes among young adult cancer survivors.
Authors: Shoshana M. Rosenberg, Ann H. Partridge, Philip Daniel Poorvu, Jacqueline N. Casillas, Patricia A. Ganz, Linda A. Jacobs, Mary S. McCabe, Linda Overholser, Steven C Palmer, Emily Jo Rajotte, Betsy C Risendal, Donald Rosenstein, Karen Leslie Syrjala, K. Scott Baker
Journal: Journal of Clinical Oncology (2018)

115 Background: Fertility is a critical survivorship issue for young adults (YA) with cancer. Data regarding use of fertility preservation (FP) and fertility outcomes in this population are limited. Methods: In 2013-2014, 868 patients, aged 18-39, 1-5 years post diagnosis (dx) of an invasive cancer completed a survey about the impacts of cancer and treatment including fertility. Descriptive statistics were used to characterize FP options pursued, reasons for not undergoing FP, and pregnancy outcomes. Logistic regression was used to identify factors associated with pre- treatment FP. Results: Median age at dx was 32. Most respondents were female (73%), married (61%), with a college degree (71%). Breast (28%), thyroid (15%), and lymphoma (13%) were the most common dx. 13% (77/614) of women and 36% (82/231) of men reported FP attempts prior to treatment, including 57% of testicular, 39% of lymphoma, 27% of leukemia, and 18% of breast cancer survivors. In men, sperm banking (96%) was the most common approach; in women, embryo (47%) and oocyte (23%) cryopreservation. Of those who did not pursue FP (N=686), 19% reported lack of information on risks/options as the reason. In multivariable analyses, FP was associated (p&lt;0.05) with male gender, younger age, chemotherapy, being married, and having a college degree; survivors who had children prior to dx were less likely to pursue FP (Table). Of 60 men who tried to father a pregnancy, 42 (70%) were successful and 37 (88%) conceived naturally. Of 114 women who attempted pregnancy, 83 (73%) were successful, 76 (92%) conceived naturally. Conclusions: Some YA patients are not aware of treatment risks and FP options, indicating that fertility may be under-addressed. In our sample, nearly all patients who reported attempting pregnancy within 5 years of dx conceived naturally, suggesting that a risk stratified approach may help optimize use of FP services. [Table: see text]
Incidence of 4 Lysosomal Storage Disorders From 4 Years of Newborn Screening
Authors: Patrick V. Hopkins, Tracy Klug, Lacey Vermette, Julie Raburn-Miller, Jami Kiesling, Sharmini Rogers
Journal: JAMA Pediatrics (2018)

Incidence of 4 Lysosomal Storage Disorders From 4 Years of Newborn ScreeningNewborn screening is recognized as a highly effective public health program to detect certain diseases before detrimental longterm health consequences occur.With advances in screening technologies and therapeutic options becoming available, the US Department of Health and Human Services recently added 2 lysosomal storage disorders (LSDs), Pompe disease and mucopolysaccharidosis I (MPS I), to the Recommended Uniform Screening Panel. 1 In addition, several states have legislative mandates to screen for other LSDs not on the Recommended Uniform Screening Panel.The Missouri State Public Health Laboratory has used a fluorimetric enzyme activity test on a digital microfluidic platform to screen all samples from newborns that were received since January 11, 2013, for Pompe, MPS I, Gaucher, and Fabry disorders. 2We herein present our findings on incidence rates for these LSDs from 4 years of full-population testing.These results represent, to our knowledge, the longest prospective, unblinded, full-population testing and follow-up for these LSDs in the United States.
Upregulation of amphiregulin on CD14++CD16- (classical) monocytes in non-small cell lung cancer.
Authors: Fiona Margaret McCarthy, Juliana Candido, Robin Rudd, Jeremy P. C. Steele, Frances Balkwill
Journal: Journal of Clinical Oncology (2017)

e14612 Background: Amphiregulin is an EGFR ligand which contributes to many of the hallmarks of cancer including angiogenesis and metastasis. Recent studies demonstrate that Amphiregulin promotes an immunosuppressive tumour microenvironment by modulating the expression of T regulatory cells. Although its expression has been described on a variety of immune cells and tumour cells, there is no published data on Amphiregulin expression by monocytes to date. Previous work by this group has demonstrated that monocytes from non-small cell lung cancer patients are phenotypically and genomically different compared to healthy volunteers. This study aims to further investigate the differing genomic profile of monocytes in non-small cell lung cancer. Methods: Gene expression profiling was performed on CD14 ++ CD16 - (classical) monocytes of newly diagnosed patients with Stage IV non-small cell lung cancer (n = 6) and age-matched healthy volunteers (n = 6) using Affymetrix Human U133 Plus 2.0 array. Validation of differentially expressed genes of interest (including Amphiregulin) at mRNA level was performed using real-time PCR with TaqMan gene expression assays on independent patient (n = 6) and healthy volunteer cohorts (n = 6). Differential protein expression of Amphiregulin from the monocytes of healthy volunteers (n = 3) and non-small cell lung cancer patients (n = 3) was validated using ELISA technology. Results: Amphiregulin is one of the most upregulated genes on classical monocytes in non-small cell lung cancer patients compared to healthy volunteers (p = 0.001). The increased expression of Amphiregulin was confirmed on qPCR validation in an independent cohort of non-small cell lung cancer patients (p &lt; 0.05) as well as in the original group (p &lt; 0.001). Amphiregulin was also found to be increased at protein level on CD14 ++ CD16 - monocytes of non-small cell lung cancer compared to healthy volunteers. (p = 0.37). Conclusions: Amphiregulin is overexpressed by classical monocytes in non-small cell lung cancer and this over-expression is confirmed at mRNA and protein level. The production of Amphiregulin has not been ascribed to human monocytes in non-small cell lung cancer making its overexpression in this study a unique finding.
Photochemical internalization enhances cytosolic release of antibiotic and increases its efficacy against staphylococcal infection
Authors: Xiaolin Zhang, Leonie de Boer, Laura Heiliegers, Sandra Man-Bovenkerk, Pål Kristian Selbo, Jan W. Drijfhout, Anders Høgset, Sebastian A.J. Zaat
Journal: Journal of Controlled Release (2018)
A meta-analysis of antiangiogenic therapy for glioblastoma (GBM).
Authors: Mustafa Khasraw, Malaka Ameratunga, Andrew B. Lassman, David M. Ashley, Helen Wheeler, Nick Pavlakis
Journal: Journal of Clinical Oncology (2014)

2047 Background: Overall Survival (OS) and Progression Free Survival (PFS) results of randomized controlled trials (RCTs) are available of anti-angiogenic therapy (AAT) in GBM, especially Bevacizumab (Bev). Methods: Searches were conducted to identify published and unpublished RCTs starting in 2000 including The Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE and EMBASE. Proceedings of relevant oncology conferences from 2000 to 1/ 2014, were also searched. RCTs with random allocation of the use of AATs to treat GBM were included. Authors screened search results and reviewed abstracts of potentially relevant articles before retrieving the full text of eligible articles. Results: Seven eligible RCTs were identified including 3187 patients. There was significant heterogeneity in studies especially in response assessment criteria. Six studies were only available in abstract form. Trials included in this analysis did not show improvement in OS with a pooled hazard ratio (HR) of 0.95 (95% CI 0.87 to 1.04; P = 0.27). They did however demonstrate improvement in PFS with improvement in the HR for PFS at 0.74 (95% CI 0.68 to 081; P= 0.00001). The HRs of the studies containing Bev as the AAT were generally more likely to report favorable results than other AAT, the pooled HR for PFS for Bev studies (n = 1712 patients) was significant at 0.57 (95% CI 0.4 to 0.82; P = 0.002). In the adjuvant setting with 5 RCTs including 2441 patients (AVAGLIO, RTOG 0825, GLARIUS with Bev; CENTRIC and CORE with cilengitide), the HR for OS was 0.90 (P = 0.19). Pooled analysis for PFS in the adjuvant setting (4 studies, n= 2441) showed significant HR at 0.69 (95% CI 0.56, 0.85; P= 0.0006). In the recurrent setting pooling of 2 RCTs (n=576) namely the phase 3 with cediranib (REGAL) and the phase 2 study with Bev (BELOB) showed HR for OS was 1.02 (P = 93). The BELOB study did not report PFS i.e., there is no RCT data to assess PFS with Bev in recurrent GBM. Conclusions: Bev appears to prolong PFS in newly diagnosed GBM. Available data does not demonstrate a survival benefit in newly diagnosed patients. In the recurrent setting, there is no adequately powered RCT to address if there is a PFS or survival benefit with Bev. A more detailed analysis is prepared as a Cochrane systematic review.
Investigation of the Relationship Between Susceptibility Loci for Hip Osteoarthritis and Dual X‐Ray Absorptiometry–Derived Hip Shape in a Population‐Based Cohort of Perimenopausal Women
Authors: Denis A. Baird, Lavinia Paternoster, Jennifer S. Gregory, Benjamin G. Faber, Fiona R. Saunders, Claudiu V. Giuraniuc, Rebecca J. Barr, Deborah A. Lawlor, Richard M. Aspden, Jonathan H. Tobias
Journal: Arthritis & Rheumatology (2018)

Objective To examine relationships between known osteoarthritis ( OA ) susceptibility loci and hip shape in a population‐based cohort of perimenopausal women in order to investigate whether hip shape contributes to OA development. Methods Hip shape was measured, using statistical shape modeling, on dual x‐ray absorptiometry scans of the hip from mothers in the Avon Longitudinal Study of Parents and Children ( ALSPAC ). The proximal femur and superior acetabulum were outlined, and independent hip shape modes were generated. In a subregional model, points were restricted to the acetabulum and superior femoral head. Associations between 11 OA ‐related single‐nucleotide polymorphisms, identified by literature search, and shape modes were analyzed in a multivariate canonical correlation analysis. Results A total of 3,111 women (mean age 48 years) had genetic and hip shape data. The KLHDC 5/ PTHLH rs10492367 OA risk allele was associated with a wider upper femur in the whole shape model ( P = 1 × 10 −5 ). The DOT 1L rs12982744 OA risk allele was associated with reduced superior joint space in the subregional shape model ( P = 2 × 10 −3 ). The COL 11A1 rs4907986 OA risk allele was associated with lateral displacement of the femoral head relative to the acetabulum in the subregional shape model ( P = 5 × 10 −4 ). Regional association plots identified an additional COL 11A1 locus in moderate linkage disequilibrium with rs4907986, which was more strongly associated with hip shape (rs10047217; P = 3 × 10 −6 ). Colocalization analysis indicated sharing of genetic signals for hip shape and hip OA for the KLHDC 5/ PTHLH and COL 11A1 loci. Conclusion Hip OA susceptibility loci were associated with shape in this study, suggesting that these loci (and potentially yet‐to‐be‐identified hip OA loci) could contribute to hip OA in later life via perturbing biologic pathways that mediate morphology development.
Abstract 13219: Dll4-Notch Signaling Mediates Vascular Inflammation and Calcification in Chronic Kidney Disease: A Novel Mechanism
Authors: Toshiaki Nakano, Angelo S Kum, Rodrigo K Kuromoto, Hiroshi Iwata, Elena Aikawa, Masanori Aikawa
Journal: Circulation (2015)

Background: Chronic kidney disease (CKD) increases cardiovascular risk. However, the underlying mechanisms remain obscure and current therapies, including statins, cannot prevent CKD-associated cardiovascular events. We previously demonstrated that the Notch signaling ligand Delta-like 4 (Dll4) promotes macrophage activation. To identify a new mechanism and therapeutic target, we investigated the causal role of the Dll4-Notch pathway in vascular inflammation in CKD. Methods &amp; Results: [In vitro] Indoxyl sulfate, a major uremic toxin, is an independent risk predictor in CKD. Clinically relevant concentrations (0.5-1.0 mM) of indoxyl sulfate increased the expression of proinflammatory molecules (e.g., IL-1β, TNFα, MCP-1), and Notch signaling components (e.g., Dll4, Notch3) in human primary macrophages derived from peripheral blood mononuclear cells. Notch inhibition with the γ-Secretase inhibitor DAPT suppressed indoxyl sulfate-triggered induction of proinflammatory molecules (e.g., MCP-1, Figure A) in macrophages. [In vivo] In LDL receptor-deficient (Ldlr-/-) mice, an established model of atherosclerosis, 5/6 nephrectomy induced renal dysfunction assessed by elevated creatinine (0.56 ± 0.05 mg/dl) and BUN (128.0 ± 1.9 mg/dl), CKD accelerated the expression of IL-1β, IL-6, TNFα, and MCP-1 in splenic macrophages, and aortic atherosclerosis and calcification in Ldlr-/- mice Suppression of Notch signaling by Dll4 antibody reduced the size of atherosclerotic lesions of the aorta (p&lt;0.05) and luminal stenosis in the brachiocephalic arteries (p&lt;0.05) in the CKD cohort as compared to mice treated by control IgG (n=14/13 per group). Dll4 antibody also decreased macrophage accumulation and early calcification (alkaline phosphatase activity) in the aorta (Figure B). Conclusion: The present study suggests that Dll4 serves as a new therapeutic target for atherosclerotic plaque inflammation and calcification in CKD.
Selective targeting of antiapoptotic BCL‐2 proteins in cancer
Authors: Ahmet Can Timucin, Huveyda Basaga, Ozgur Kutuk
Journal: Medicinal Research Reviews (2018)

Circumvention of apoptotic machinery is one of the distinctive properties of carcinogenesis. Extensively established key effectors of such apoptotic bypass mechanisms, the antiapoptotic BCL-2 (apoptosis regulator BCL-2) proteins, determine the response of cancer cells to chemotherapeutics. Within this background, research and development of antiapoptotic BCL-2 inhibitors were considered to have a tremendous amount of potential toward the discovery of novel pharmacological modulators in cancer. In this review, milestone achievements in the development of selective antiapoptotic BCL-2 proteins inhibitors for BCL-2, BCL-XL (BCL-2-like protein 1), and MCL-1 (induced myeloid leukemia cell differentiation protein MCL-1) were summarized and their future implications were discussed. In the first section, the design and development of BCL-2/BCL-XL dual inhibitor navitoclax, as well as the recent advances and clinical experience with selective BCL-2 inhibitor venetoclax, were synopsized. Preclinical data from selective BCL-XL inhibitors, which are currently undergoing extensive testing as a single agent or in combination with other therapeutic agents, were further summarized. In the second section, MCL-1 inhibitors developed as potential anticancer agents were reviewed regarding their specificity toward MCL-1. Explicitly, studies leading to the identification of MCL-1, nonselective and selective targeting of MCL-1, and recently initiated clinical trials were compiled in chronological order. Based on these concepts, future directions were further discussed for increasing selectivity in the design of prosurvival BCL-2 member inhibitors.
Targeting phosphatases of regenerating liver (PRLs) in cancer
Authors: Min Wei, Konstantin V. Korotkov, Jessica S. Blackburn
Journal: Pharmacology & Therapeutics (2018)

The phosphatase of regenerating liver (PRL) family, also known as protein tyrosine phosphatase 4A (PTP4A), are dual-specificity phosphatases with largely unknown cellular functions. However, accumulating evidence indicates that PRLs are oncogenic across a broad variety of human cancers. PRLs are highly expressed in advanced tumors and metastases compared to early stage cancers or matched healthy tissue, and high expression of PRLs often correlates with poor patient prognosis. Consequentially, PRLs have been considered potential therapeutic targets in cancer. Persistent efforts have been made to define their role and mechanism in cancer progression and to create specific PRL inhibitors for basic research and drug development. However, targeting PRLs with small molecules remains challenging due to the highly conserved active site of protein tyrosine phosphatases and a high degree of sequence similarity between the PRL protein families. Here, we review the current PRL inhibitors, including the strategies used for their identification, their biological efficacy, potency, and selectivity, with a special focus on how PRL structure can inform future efforts to develop specific PRL inhibitors.