tbuckley/cabot-search huggingface dataset:
Kidney-targeted rhein-loaded liponanoparticles for diabetic nephropathy therapy via size control and enhancement of renal cellular uptake
Authors: Guowei Wang, Qunying Li, Danfei Chen, Bihan Wu, Yulian Wu, Weijun Tong, Pintong Huang
Journal: Theranostics (2019)

The optimization of nanoparticle size for passing through glomerular filtration membrane, inefficient renal cellular uptake and rapid urinary excretion of nanoparticles are the major obstacles for renal disease treatment via a nanoparticle delivery system. Herein, we propose a concept of a two-step nanoparticular cascade of size control and enhancement of renal cellular uptake to overcome the renal delivery obstacles. Methods: We prepared kidney-targeted rhein (RH)-loaded liponanoparticles (KLPPR) with a yolk-shell structure composed by polycaprolactone-polyethyleneimine (PCL-PEI)-based cores and kidney targeting peptide (KTP)-modified lipid layers. The KLPPR size within the range of 30 ~ 80 nm allowed KLPPR distribute into kidney by passing through the glomerular filtration membrane and the KTP (sequence: CSAVPLC) decoration promoted the renal cellular uptake and endocytosis via a non-lysosomal pathway. Results: The KLPPR had an average size of 59.5±6.2 nm and exhibited high RH loading, sustained release, good stability and biocompatibility, rapid cellular uptake in HK-2 cells. In addition, intravenous administration of KLPPR resulted in excellent kidney-targeted distribution and low urinary excretion in mice with streptozocin-induced diabetic nephropathy (DN), lowered the parameters of urea nitrogen, serum creatinine and kidney index, as well as facilitated the recovery of renal physiological function in improving the levels of urinary creatinine and the creatinine clearance rate by suppressing secretion and accumulation of fibronectin and TGF-β1. Conclusion: Definitely, KLPPR were able to target the diseased kidney and improve the therapeutic effect of RH on DN by exploiting the two-step nanoparticular cascade of size control and enhancement of cellular uptake. This study offers a promising strategy for renal diseases treatment using liponanoparticle delivery system.
Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules
Authors: Angeliki P. Kourounakis, Dimitrios Xanthopoulos, Ariadni Tzara
Journal: Medicinal Research Reviews (2019)

Abstract Morpholine is a heterocycle featured in numerous approved and experimental drugs as well as bioactive molecules. It is often employed in the field of medicinal chemistry for its advantageous physicochemical, biological, and metabolic properties, as well as its facile synthetic routes. The morpholine ring is a versatile and readily accessible synthetic building block, it is easily introduced as an amine reagent or can be built according to a variety of available synthetic methodologies. This versatile scaffold, appropriately substituted, possesses a wide range of biological activities. There are many examples of molecular targets of morpholine bioactive in which the significant contribution of the morpholine moiety has been demonstrated; it is an integral component of the pharmacophore for certain enzyme active‐site inhibitors whereas it bestows selective affinity for a wide range of receptors. A large body of in vivo studies has demonstrated morpholine's potential to not only increase potency but also provide compounds with desirable drug‐like properties and improved pharamacokinetics. In this review we describe the medicinal chemistry/pharmacological activity of morpholine derivatives on various therapeutically related molecular targets, attempting to highlight the importance of the morpholine ring in drug design and development as well as to justify its classification as a privileged structure.
Postmenopausal Estrogen Therapy and Cardiovascular Disease
Authors: Meir J. Stampfer, Graham A. Colditz, Walter C. Willett, JoAnn E. Manson, Bernard Rosner, Frank E. Speizer, Charles H. Hennekens
Journal: New England Journal of Medicine (1991)

The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. Our 1985 report in the Journal, based on four years of follow-up, suggested that estrogen therapy reduced the risk of coronary heart disease, but a report published simultaneously from the Framingham Study suggested that the risk was increased. In addition, studies of the effect of estrogens on stroke have yielded conflicting results.
Unpacking clinical trial offers: A qualitative analysis of interactions with physicians and patients potentially eligible for a prostate cancer trial.
Authors: Lauren M. Hamel, David W. Dougherty, Mark A. Manning, Louis Penner, Terrance Lynn Albrecht, Elisabeth I. Heath, Michael Anthony Carducci, Dina Lansey, Seongho Kim, Susan Eggly
Journal: Journal of Clinical Oncology (2019)

e23169 Background: Clinical trial accrual among cancer patients is low (2-5%). More data are needed to identify barriers to enrollment and inform interventions. One way to identify the greatest barriers is by examining clinical interactions. We investigated whether and under what circumstances patients potentially eligible for a trial at a major cancer center were offered the chance to enroll. Methods: We conducted a qualitative content analysis of 50 recorded interactions with physicians (n = 8) and patients (n = 36) with intermediate- or high-risk prostate cancer who were initially eligible for a trial at two NCI-designated comprehensive cancer centers. We observed and coded the interactions in three steps: 1) classification of all interactions as explicit offer, offer pending, trial discussed but not offered, or trial not discussed; 2) in interactions with no explicit offer, classification of patients who were informed their disease was stable or had progressed; 3) in interactions classified as cancer progressed but no trial offered, identification of factors discussed that may explain the lack of an offer. Results: Of the 50 interactions, 30% were classified as explicit offer; 6% as offer pending; 18% as trial discussed but not offered; and 40% as trial not discussed. Of the 35 interactions with no offer, 54% were with patients whose cancer had not progressed. In the 16 remaining interactions with patients with no offer and whose cancer had progressed, reasons for the lack of offer included: testing needed, no trial/study slot, and comorbidities; but in 25% of these, no reason was provided. Conclusions: Even in this highly selected population, few patients were offered a trial, often because they were ultimately ineligible. Findings support professional recommendations to broaden inclusion criteria to increase the pool of eligible patients. Findings also suggest trial accrual rates could be more accurately calculated by considering patients who are eligible to enroll, rather than all patients with cancer. In 40% of interactions, there was no mention of a trial, suggesting interventions should also be aimed at patient and physician attitudes and clinical communication. Clinical trial information: NCT 02906241.
Cautiously optimistic rationalism may not be cautious enough
Authors: Justin F Landy
Journal: Behavioral and Brain Sciences (2019)

Abstract May expresses optimism about the source, content, and consequences of moral judgments. However, even if we are optimistic about their source (i.e., reasoning), some pessimism is warranted about their content, and therefore their consequences. Good reasoners can attain moral knowledge, but evidence suggests that most people are not good reasoners, which implies that most people do not attain moral knowledge.
CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease
Authors: Gary L. Myers, Nader Rifai, Russell P. Tracy, William L. Roberts, R. Wayne Alexander, Luigi M. Biasucci, John D. Catravas, Thomas G. Cole, Gerald R. Cooper, Bobby V. Khan, Mary M. Kimberly, Evan A. Stein, Kathryn A. Taubert, G. Russell Warnick, Parvin P. Waymack
Journal: Circulation (2004)

HomeCirculationVol. 110, No. 25CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease
Copper-incorporated bioactive glass-ceramics inducing anti-inflammatory phenotype and regeneration of cartilage/bone interface
Authors: Rongcai Lin, Cuijun Deng, Xuxiang Li, Yaqin Liu, Meng Zhang, Chen Qin, Qingqiang Yao, Liming Wang, Chengtie Wu
Journal: Theranostics (2019)

Osteoarthritis not only results in cartilage lesion, but also is accompanied with subchondral bone damage caused by the inflammatory response. It is of great significance to treat osteoarthritis by regulating the immune response. As copper (Cu) plays an essential role in immune response and anti-arthritis, a copper-incorporated bioactive glass-ceramics (Cu-BGC) may achieve the aim of healing cartilage lesion and reducing inflammatory response caused by osteoarthritis. We hypothesized that the Cu2+ released from Cu-BGC scaffolds may satisfy the requirements of cartilage regeneration and anti-arthritis. Methods: 3D-printing method was employed to prepare Cu-BGC scaffolds. The stimulating effect on the chondrocytes and macrophages cultured with Cu-BGC extracts was investigated. Furthermore, the in vivo regenerative effect of Cu-BGC scaffolds on osteochondral defects was studied. Results: The incorporation of Cu2+ into BGC considerably promoted the proliferation and maturation of chondrocytes, and induced macrophages shifting to anti-inflammatory phenotype. Histological analysis demonstrated that the Cu-BGC scaffolds meaningfully improved the regeneration of cartilage and elevated the recovery of the osteochondral interface as compared with the CTR and BGC groups. The potential mechanism is related to Cu2+ ions triggering the immune response of cartilage via activating HIF signaling pathway and inhibiting the inflammatory response in osteochondral tissue. Conclusion: These results demonstrated that Cu-BGC scaffolds significantly facilitated the regeneration of cartilage and osteochondral interface, as well as inhibited inflammatory response, which may prevent the development of osteoarthritis associated with osteochondral defects.
Risk factors of psychological distress and quality of life in lung cancer patients.
Authors: Fan Zhang, Junyan Wang, Lei Hong, Yu Xu, Da Jiang, Suju Wei
Journal: Journal of Clinical Oncology (2019)

e23187 Background: Most patients with lung cancer have psychological problems, which has a significant impact on patients' rehabilitation, treatment and quality of life. Through the distress and quality of life assessment, to understand the risk factors of distress, in order to improve the quality of life of lung cancer patients. Methods: The investigation was consisted of 209 lung cancer patients who were treated in Fourth Hospital of Hebei Medical University from February 2014 to December 2015.Patients were assessed through the use of distress thermometer, problem list, quality of life questionnaire. Lung cancer patients were divided into a significant distress group and a non-significant distress group. Chi-square test was used to analyze the relationship between demographic characteristics, disease information and significant distress. Logistic regression analysis was used to analyze risk factors for distress. The Spearman rank correlation was used to analyze the correlation between the significant distress group and each area of the quality of life questionnaire. The test level was significantly different at P&lt; 0.05. Results: The distress of majority lung cancer patients was 0-4 points, 68 cases were significant distress, significant distress rate was 32.5%. Logistic regression showed PS scores, family residence, informed condition were risk factors of significant distress( P&lt; 0.001 &lt; P= 0.035, P= 0.031). Economic problems were the most common cause of psychological distress in lung cancer patients. Other risk factors included the lack of time and energy to take care for the elderly/children, fear, sadness, dizziness and pain. The significant distress of lung cancer patients was negatively correlated with health status, physical function, emotional function, cognitive function, social function, and was positively correlated with symptoms as fatigue, nausea and vomiting, pain, shortness of breath, insomnia, loss of appetite and constipation. Conclusions: The incidence of significant distress in patients with lung cancer is 32.5%. PS score, fully informed, and family residence are the risks of significant distress in patients. The distress of lung cancer patients is significantly related to the quality of life.
Impact of combination HIV interventions on HIV incidence in hyperendemic fishing communities in Uganda: a prospective cohort study
Authors: Joseph Kagaayi, Larry W Chang, Victor Ssempijja, M Kate Grabowski, Robert Ssekubugu, Gertrude Nakigozi, Godfrey Kigozi, David M Serwadda, Ronald H Gray, Fred Nalugoda, Nelson K Sewankambo, Lisa Nelson, Lisa A Mills, Donna Kabatesi, Stella Alamo, Caitlin E Kennedy, Aaron A R Tobian, John S Santelli, Anna Mia Ekström, Helena Nordenstedt, Thomas C Quinn, Maria J Wawer, Steven J Reynolds
Journal: The Lancet HIV (2019)
Pregnant Women With Uncorrected Congenital Heart Disease
Authors: Karen Sliwa, Lucia Baris, Christoph Sinning, Elvin Zengin-Sahm, Lina Gumbiene, Israa F. Yaseen, Ghada Youssef, Mark Johnson, Hasan Al-Farhan, Malgorzata Lelonek, Roger Hall, Jolien Roos-Hesselink
Journal: JACC Heart Failure (2019)
Trisomy 8 Remains An Intermediate Cytogenetic Risk Factor in Patients with Acute Myeloid Leukemia (AML) Treated with Stem Cell Transplantation
Authors: Claudia Ulrike Walter, Fahed Almhareb, Naeem A. Chaudhri, Hazzaa Al Zahrani, Mohammad Bakr, Khalid Ibrahim, Fazal Hussain, Said Mohamed, Walid Rasheed, Fahad Alsharif, Mahmoud Aljurf, Maher Albitar
Journal: Blood (2011)
Intrusive imagery associated with pain
Authors: Christopher J Graham, Shona L Brown, Katy Vincent, Andrew W Horne
Journal: BMJ (2019)

Warren describes the use of example imagery to help patients describe their pain experience, which should substantially improve doctor-patient communication.1 Padfield and colleagues explored the same clinical tool in their engaging perspective piece.2 They describe a therapeutic triangle linking the clinician, patient, and image and showcase the revealing patient narratives generated. One patient selected an image of a broken link in a chain and used this to discuss her feelings …
Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk, Elderly Patients With Severe Aortic Stenosis
Authors: Jin Kyung Oh, Sung-Ji Park, Ho Jin Kim, Jung-Min Ahn, Dae-Hee Kim, Hyeon-Cheol Gwon, Pyo Won Park, Duk-Hyun Kang, Duk-Woo Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2019)
Climate crisis: healthcare is a major contributor, global report finds
Authors: Raffaella Bosurgi
Journal: BMJ (2019)

The global healthcare sector’s carbon footprint is equivalent to 4.4% of global net emissions, making it a major contributor to the climate crisis, a landmark international report1 has found.

If the healthcare sector was a country it would be the fifth largest emitter on the planet, the report by the non-governmental organisation Health Care Without Harm and the consultancy firm Arup found.

The report, launched at the Wellcome Trust in London on 10 September, analysed spending and other data from 43 …
NSD1 and NSD2 Transcriptional Levels Might Predict Clinical Outcome in AML Patients
Authors: Virginia Mara De Deus Wagatsuma, Diego Antonio Pereira-Martins, Mariane Cristina Do Nascimento, Silvia Elena Sanchez Mendoza, Antonio R. Lucena-Araujo, Aleide Lima, Felipe Saldanha-Araujo, Fabio Pitella, Fabiola Traina, Maria Isabel A Madeira, Lorena Lobo Figueiredo-Pontes, Eduardo Magalhães Rego
Journal: Blood (2018)
Orbital Adult T-Cell Leukemia/lymphoma With Skin Involvement Demonstrated on FDG PET/CT
Authors: Masatoshi Hotta, Ryogo Minamimoto
Journal: Clinical Nuclear Medicine (2019)

Abstract An 85-year-old woman presented with decreased visual acuity. MRI of the brain revealed bilateral orbital masses, and FDG-PET/CT demonstrated moderate to intense uptake in the orbital tumors and thickened skin on the left lower leg. Biopsies of the orbital and cutaneous lesions revealed infiltration by T-cell lymphoma, and the presence of human T-cell lymphotropic virus type 1 antigens confirmed the diagnosis of adult T-cell leukemia/lymphoma (ATLL). Although orbital ATLL is rare, the skin is a common site of extranodal involvement of T-cell lymphomas, including ATLL, and FDG uptake by a cutaneous lesion can facilitate early diagnosis.
After stroke due to ICH while on antithrombotics, starting vs avoiding antiplatelets did not differ for symptomatic ICH
Authors: Jeremy Graham
Journal: Annals of Internal Medicine (2019)

ACP Journal Club17 September 2019After stroke due to ICH while on antithrombotics, starting vs avoiding antiplatelets did not differ for symptomatic ICHJeremy Graham, DO, MA, FACPJeremy Graham, DO, MA, FACPElson S. Floyd College of Medicine, Washington State University Spokane, Spokane, Washington, USA (J.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ201909170-032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationRESTART Collaboration. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Lancet. 2019;393:2613-23. https://pubmed.ncbi.nlm.nih.gov/31128924Clinical Impact RatingsHematology: References1 Nielsen PB, Larsen TB, Skjøth F, et al. Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: a nationwide cohort study. Circulation. 2015;132:517-25. [PMID: 26059010] Google Scholar2 Casaubon LK, Boulanger JM, Blacquiere D, et al; Heart and Stroke Foundation of Canada Canadian Stroke Best Practices Advisory Committee. Canadian stroke best practice recommendations: hyperacute stroke care guidelines, update 2015. Int J Stroke. 2015;10:924-40. [PMID: 26148019] Google Scholar3 Al-Shahi Salman R, Dennis MS, Murray GD, et al; RESTART collaborators. The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial. Trials. 2018;19:162. [PMID: 29506580] Google Scholar Author, Article, and Disclosure InformationAffiliations: Elson S. Floyd College of Medicine, Washington State University Spokane, Spokane, Washington, USA (J.G.)This article was published at Annals.org on 3 September 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 September 2019Volume 171, Issue 6Page: JC32KeywordsAntiplatelet therapyDrug therapyHemorrhagic strokeIschemic strokeMyocardial infarctionPulmonary embolismQuality of lifeRevascularizationStroke ePublished: 17 September 2019 Issue Published: 17 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A model-based approach to optimize detection of treatment effects in early oncology trials.
Authors: Sylvie Retout, Alex Phipps, David Geho, Jean Tessier, Gwen L. Nichols, Dean Bottino
Journal: Journal of Clinical Oncology (2013)

e13508 Background: Tumor size change from baseline (RECIST) is often used to assess antitumor activity of investigational agents in phase 1 trials, but this measure does not take into account the tumor growth rate (TGR) prior to treatment. TGR could be highly variable in a phase 1 ‘all-comers’ patient population, with a high TGR potentially masking a meaningful treatment effect (TE). Assessing the change in TGR (Mehrara et al, BJC 2011) using historical tumor burden assessments (Gomez-Roca et al, Eur J Cancer 2011) may provide higher sensitivity to true TE (TTE). The objectives of the current study are to formalize a Growth Rate Based Method (GRBM) and to compare, using simulated patients, the ability of GRBM and RECIST assessments to detect and quantify TTE. Methods: The exponential tumor growth model (Claret et al, J Clin Oncol. 2009) was used to simulate the sum of the longest diameters (SLD) individual time courses of 2000 virtual patients under different TGR scenarios: slow, medium, fast and ‘all comers’ (highly variable TGR as often encountered in phase 1). Different sampling designs were simulated wherein tumor assessments with measurement errors were obtained, ranging from 16 to 4 weeks prior to treatment initiation (TI), immediately before TI, and 8 and 16 weeks after TI. TTE was defined as the difference between the simulated SLDs at 16 weeks with and without treatment. GRBM response was defined as the model-predicted difference between the SLDs with and without treatment, as estimated from the simulated samples. Sensitivity (Se) of RECIST or GRBM was defined as the probability of classifying a patient as a RECIST or GRBM &gt;30% reduction when the TTE &gt;30%, and specificity (Sp) as the probability of RECIST or GRBM reduction &lt;30% when TTE &lt;30%. Results: RECIST Se was consistently inferior to GRBM, notably in the all-comers TGR (37% vs 74-89%) scenario. GRBM maintained Se (71-89%) irrespective of TGR whereas RECIST Se degraded significantly with increasing TGR. RECIST Sp was high (97-100%) while GRBM Sp was lower (55-80%) depending on sampling design and TGR. Conclusions: Incorporation of an additional pretreatment tumor assessment by GRBM may augment RECIST by increasing sensitivity to TTE, particularly in a heterogeneous TGR phase 1 setting.
Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer
Authors: Wolfgang P. Fendler, Manuel Weber, Amir Iravani, Michael S. Hofman, Jérémie Calais, Johannes Czernin, Harun Ilhan, Fred Saad, Eric J. Small, Matthew R. Smith, Paola M. Perez, Thomas A. Hope, Isabel Rauscher, Anil Londhe, Angela Lopez-Gitlitz, Shinta Cheng, Tobias Maurer, Ken Herrmann, Matthias Eiber, Boris Hadaschik
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Systemic androgen-signaling inhibition added to ongoing androgen-deprivation therapy (ADT) improved clinical outcomes in patients with nonmetastatic castration-resistant prostate cancer without detectable metastases by conventional imaging (nmCRPC). Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) detects prostate cancer with superior sensitivity to conventional imaging, but its performance in nmCRPC remains largely unknown. We characterized cancer burden in high-risk patients with nmCRPC using PSMA-PET. Experimental Design: We retrospectively included 200 patients with nmCRPC, prostate-specific antigen (PSA) &amp;gt;2 ng/mL, and high risk for metastatic disease [PSA doubling time (PSADT) of ≤10 months and/or Gleason score of ≥8] from six high-volume PET centers. We centrally reviewed PSMA-PET detection rate for pelvic disease and distant metastases (M1). We further evaluated SPARTAN patients stratified by risk factors for PSMA-PET-detected M1 disease. Results: PSMA-PET was positive in 196 of 200 patients. Overall, 44% had pelvic diseases, including 24% with local prostate bed recurrence, and 55% had M1 disease despite negative conventional imaging. Interobserver agreement was very high (κ: 0.81–0.91). PSA ≥ 5.5 ng/mL, locoregional nodal involvement determined by pathology (pN1), prior primary radiation, and prior salvage radiotherapy independently predicted M1 disease (all P &amp;lt; 0.05). Conclusions: PSMA-PET detected any disease in nearly all patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSADT of ≤10 months and Gleason score of ≥8. The value of PSMA-PET imaging for treatment guidance should be tested in future studies.