tbuckley/cabot-search huggingface dataset:
Biodegradable <sup>131</sup>Iodine‐Labeled Microspheres: Potential Transarterial Radioembolization Biomaterial for Primary Hepatocellular Carcinoma Treatment
Authors: Fuwen Pang, Yuhao Li, Wenjie Zhang, Chunchao Xia, Qing He, Zhenlin Li, Liu Xiao, Simin Song, Ping Dong, Huijun Zhou, Tuo Shao, Huawei Cai, Lin Li
Journal: Advanced Healthcare Materials (2020)

Abstract Transarterial radioembolization with radionuclide‐labeled microspheres is successfully used in hepatocellular carcinoma (HCC) treatment, but the non‐biodegradability and rapid settlement of the microsphere material are associated with unsatisfied distribution and unable for multiple administrations. In this study, a novel biodegradable chitosan–collagen composite microsphere (CCM) with ideal settlement rate is prepared. The Fourier‐transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) results indicate CCMs have desirable shapes with diameters around 10 µm, and considerable biodegradability within 12 weeks. These CCMs are successfully radiolabeled with 131 I and processed efficiency of 70.4 MBq mg −1 of microspheres as well as favorable stability in vitro. Then, 131 I‐CCMs are injected into rats with orthotopic HCC via the hepatic artery which effectively improves the median overall survival from 19 to 44 days ( p &lt; 0.05). Single photon emission computed tomography (SPECT/CT) imaging and immunohistochemical analysis indicate well‐localized biodistribution and consistent stability of 131 I‐CCMs in the liver over 28 days. Magnetic resonance imaging (MRI) and gross specimens monitoring confirm the inhibited tumor growth after 131 I‐CCMs treatment. In conclusion, these biodegradable 131 I‐CCMs exhibit optimal radiolabeling efficiency, stability, and favorably radioembolization effect for orthotopic HCC in a rodent model, suggesting potential for interventional cancer therapy.
Cell culture dimensionality influences mesenchymal stem cell fate through cadherin-2 and cadherin-11
Authors: Fiona R. Passanha, Thomas Geuens, Simon Konig, Clemens A. van Blitterswijk, Vanessa LS. LaPointe
Journal: Biomaterials (2020)

The acquisition of a specific cell fate is one of the core aims of tissue engineering and regenerative medicine. Significant evidence shows that aggregate cultures have a positive influence on cell fate decisions, presumably through cell-cell interactions, but little is known about the specific mechanisms. To investigate the difference between cells cultured as a monolayer and as aggregates, we started by looking at cadherin expression, an important protein involved in cell adhesion, during the differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in aggregate and monolayer cultures. We observed that proliferating hMSCs in monolayer culture expressed lower levels of cadherin-2 and increased cadherin-11 expression at cell-cell contact sites over time, which was not evident in the aggregate cultures. By knocking down cadherin-2 and cadherin-11, we found that both cadherins were required for adipogenic differentiation in a monolayer as well as aggregate culture. However, during osteogenic differentiation, low levels of cadherin-2 were found to be favorable for cells cultured as a monolayer and as aggregates, whereas cadherin- 11 was dispensable for cells cultured as aggregates. Together, these results provide compelling evidence for the important role that cadherins play in regulating the differentiation of hMSCs and how this is affected by the dimensionality of cell culture.
Editorial: Physostigmine: value in treatment of central toxic effects of anti-cholinergic drugs
Authors: H. H. Hussey
Journal: JAMA (1975)

In the current issue of<i>Archives of General Psychiatry</i>(23:375-380, 1975), Granacher and Baldessarini note that a number of drugs that have anticholinergic action, in addition to provoking peripheral manifestations, can have serious toxic effects on the central nervous system, characterized by delirium, anxiety, hyperactivity, hallucinations, disorientation, and seizures. The list of drugs is long and includes antidepressants, antipsychotic drugs, antihistamines, antispasmodics, and antiparkinsonian agents. Granacher and Baldessarini believe that too few psychiatrists are aware that administration of physostigmine salicylate parenterally is the specific treatment for the central toxic effects of anticholinergic agents. Although relief of peripheral effects can be attained by administering other cholinergic drugs, they have no action on the central toxic effects because they do not cross the blood-brain barrier, which is something physostigmine does easily. To support their view on the value of physostigmine, the authors report four cases in which patients developed central anticholinergic toxic
Severe COVID-19 and related hyperferritinaemia: more than an innocent bystander?
Authors: Piero Ruscitti, Onorina Berardicurti, Antonio Barile, Paola Cipriani, Yehuda Shoenfeld, Annamaria Iagnocco, Roberto Giacomelli
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Abstract</h3> Climate change is impacting ecosystem structure and function, with potentially drastic downstream effects on human and animal health. Emerging zoonotic diseases are expected to be particularly vulnerable to climate and biodiversity disturbance. Anthrax is an archetypal zoonosis that manifests its most significant burden on vulnerable pastoralist communities. The current study sought to investigate the influence of temperature increases on the landscape suitability of anthrax in the temperate, boreal, and arctic North, where observed climate impact has been rapid. This study also explored the influence of climate relative to more traditional factors, such as livestock distribution, ungulate biodiversity, and soil-water balance, in demarcating high risk landscapes. Machine learning was used to model landscape suitability as the ecological niche of anthrax in northern latitudes. The model identified climate, livestock density and wild ungulate species richness as the most influential landscape features in predicting suitability. These findings highlight the significance of warming temperatures for anthrax ecology in northern latitudes, and suggest potential mitigating effects of interventions targeting megafauna biodiversity conservation in grassland ecosystems, and animal health promotion among small to midsize livestock herds. <h3>Significance Statement</h3> We present evidence that a warming climate may be associated with the current distribution of anthrax risk in the temperate, boreal, and arctic North. Moreover, projected warming over the coming decades was associated with substantive expansion of this risk. In addition, livestock distribution, ungulate biodiversity, and soil-water balance were also influential to anthrax risk. While these results are sobering for the future health of livestock and pastoralist communities in the northern latitudes, the coincident modulating effect of ungulate biodiversity may suggest targeted ecosystem conservation as a possible buffer against a growing anthrax niche.
The noncalcemic analogue of vitamin D, 22-oxacalcitriol, suppresses parathyroid hormone synthesis and secretion.
Authors: A J Brown, C R Ritter, J L Finch, J Morrissey, K J Martin, E Murayama, Y Nishii, E Slatopolsky
Journal: Journal of Clinical Investigation (1989)

1,25-Dihydroxyvitamin D (1,25-(OH)2D3) directly suppresses the secretion and synthesis of PTH in vivo and in cell culture. This compound has been used to treat secondary hyperparathyroidism associated with renal failure, but in some patients prolonged treatment with 1,25-(OH)2D3 results in hypercalcemia. An analogue of 1,25-(OH)2D3 with little or no calcemic activity, 22-oxacalcitriol (OCT), was recently developed. We confirmed this lack of calcemic activity by acute and chronic administration to normal rats. A single intraperitoneal injection of vehicle (propylene glycol), OCT, or 1,25-(OH)2D3 (1.0 micrograms/rat) increased calcium by 0.32, 0.30, and 1.40 mg/dl, respectively. When rats were given daily injections of vehicle or 0.5 micrograms of either 1,25-(OH)2D3 or OCT for 4 d, calcium did not change in the rats receiving vehicle or OCT, but increased from 8.4 to 11.4 mg/dl in the rats treated with 1,25-(OH)2D3. In primary cultures of bovine parathyroid cells, 10 nM OCT was as active as 10 nM 1,25-(OH)2D3, suppressing PTH release by 33%. This suppression is due, at least in part, to blocking of transcription of the PTH gene. Using a probe prepared by random prime labeling of an Msp I fragment of plasmid PTHm122, we found that a single 40-ng dose of OCT or 1,25-(OH)2D3 depressed PTH mRNA levels by 70-80% by 48 h when compared with vehicle. Thus, OCT is a very effective suppressor of PTH secretion with virtually no calcemic activity. This analogue may be a valuable tool for the treatment of secondary hyperparathyroidism.
Corrigendum to ‘EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer—An International Collaborative Multistakeholder Effort Under the Auspices of the EAU-ESMO Guidelines Committees’ [European Urology 77 (2020) 223–250]
Authors: J. Alfred Witjes, Marek Babjuk, Joaquim Bellmunt, H. Maxim Bruins, Theo M. De Reijke, Maria De Santis, Silke Gillessen, Nicholas James, Steven Maclennan, Juan Palou, Tom Powles, Maria J. Ribal, Shahrokh F. Shariat, Theo Van Der Kwast, Evanguelos Xylinas, Neeraj Agarwal, Tom Arends, Aristotle Bamias, Alison Birtle, Peter C. Black, Bernard H. Bochner, Michel Bolla, Joost L. Boormans, Alberto Bossi, Alberto Briganti, Iris Brummelhuis, Max Burger, Daniel Castellano, Richard Cathomas, Arturo Chiti, Ananya Choudhury, Eva Compérat, Simon Crabb, Stephane Culine, Berardino De Bari, Willem De Blok, Pieter J.L. De Visschere, Karel Decaestecker, Konstantinos Dimitropoulos, Jose L. Dominguez-Escrig, Stefano Fanti, Valerie Fonteyne, Mark Frydenberg, Jurgen J. Futterer, Georgios Gakis, Bogdan Geavlete, Paolo Gontero, Bernhard Grubmüller, Shaista Hafeez, Donna E. Hansel, Arndt Hartmann, Dickon Hayne, Ann M. Henry, Virginia Hernandez, Harry Herr, Ken Herrmann, Peter Hoskin, Jorge Huguet, Barbara A. Jereczek-Fossa, Rob Jones, Ashish M. Kamat, Vincent Khoo, Anne E. Kiltie, Susanne Krege, Sylvain Ladoire, Pedro C. Lara, Annemarie Leliveld, Estefania Linares-Espinós, Vibeke Løgager, Anja Lorch, Yohann Loriot, Richard Meijer, M. Carmen Mir, Marco Moschini, Hugh Mostafid, Arndt-Christian Müller, Christoph R. Müller, James N’Dow, Andrea Necchi, Yann Neuzillet, Jorg R. Oddens, Jan Oldenburg, Susanne Osanto, Wim J.G. Oyen, Luís Pacheco-Figueiredo, Helle Pappot, Manish I. Patel, Bradley R. Pieters, Karin Plass, Mesut Remzi, Margitta Retz, Jonathan Richenberg, Michael Rink, Florian Roghmann, Jonathan E. Rosenberg, Morgan Rouprêt, Olivier Rouvière, Carl Salembier, Antti Salminen, Paul Sargos, Shomik Sengupta, Amir Sherif, Robert J. Smeenk, Anita Smits, Arnulf Stenzl, George N. Thalmann, Bertrand Tombal, Baris Turkbey, Susanne Vahr Lauridsen, Riccardo Valdagni, Antoine G. Van Der Heijden, Hein Van Poppel, Mihai D. Vartolomei, Erik Veskimäe, Antoni Vilaseca, Franklin A. Vives Rivera, Thomas Wiegel, Peter Wiklund, Peter-Paul M. Willemse, Andrew Williams, Richard Zigeuner, Alan Horwich
Journal: European Urology (2020)
Reply to Wei Liu, Xiaoping Liu, Sheng Li’s Letter to the Editor, re: Robert A. Huddart, Emma Hall, Rebecca Lewis, et al. Patient-reported Quality of Life Outcomes in Patients Treated for Muscle-invasive Bladder Cancer with Radiotherapy ± Chemotherapy in the BC2001 Phase III Randomised Controlled Trial. Eur Urol 2020;77:260–8
Authors: Robert Huddart, Emma Hall, Rebecca Lewis, Nuria Porta, Syed A. Hussain, Nicholas D. James
Journal: European Urology (2020)
Nutrition and the ageing brain: Moving towards clinical applications
Authors: Emma Flanagan, Daniel Lamport, Lorraine Brennan, Philip Burnet, Vittorio Calabrese, Stephen C. Cunnane, Martijn C. de Wilde, Louise Dye, Jonathan A. Farrimond, Nancy Emerson Lombardo, Tobias Hartmann, Thomas Hartung, Marko Kalliomäki, Gunther G. Kuhnle, Giorgio La Fata, Aleix Sala-Vila, Cécilia Samieri, A. David Smith, Jeremy P.E. Spencer, Sandrine Thuret, Kieran Tuohy, Silvia Turroni, Wim Vanden Berghe, Martin Verkuijl, Karin Verzijden, Mary Yannakoulia, Lucie Geurts, David Vauzour
Journal: Ageing Research Reviews (2020)

The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development. This overview summarises the main themes discussed during the 3rd Symposium on "Nutrition for the Ageing Brain: Moving Towards Clinical Applications" held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future. Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. The emergence of new avenues for exploring the role of diet in healthy ageing, such as the impact of the gut microbiome and development of new techniques (imaging measures of brain metabolism, metabolomics, biomarkers) are enabling researchers to approach finding answers to these questions. But the translation of these findings into clinical and public health contexts remains an obstacle due to significant shortcomings in nutrition research or pressure on the scientific community to communicate recommendations to the general public in a convincing and accessible way. Some promising programs exist but further investigation to improve our understanding of the mechanisms by which nutrition can improve brain health across the human lifespan is still required.
13P HER2 low testing in breast cancer: How to optimize detection
Authors: F. Cecchi, D. Carrolle, M. Gustavson, S. Sridhar, M. de los Reyes, S. Thyparambil, A. Bhalkikar, W-L. Liao, S. Coats, T. Hembrough
Journal: Annals of Oncology (2020)
How to Support Patient and Family in Dealing with Ethical Issues? The Relevance of Moral Case Deliberation
Authors: Guy Widdershoven, Margreet Stolper, Bert Molewijk, Suzanne Metselaar
Journal: The American Journal of Bioethics (2020)

The article of Cho et al. (2020) addresses an understudied topic in bioethics, namely ethical issues experienced by patients and family members. What stands out from the results is that patients an...
Scheduled Analgesics
Authors: THOMAS F. BECKNER
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 December 1973Scheduled AnalgesicsTHOMAS F. BECKNER, M.D.THOMAS F. BECKNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-6-913_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I recently reread the commendable February 1973 article, "Undertreatment of Medical Inpatients With Narcotic Analgesics," by Marks and Sachar (Ann Intern Med78:173-181, 1973), and once again found myself in agreement with the positions they took in their paper. Although their points speak for themselves, I have one or two observations to add that might be of some practical clinical importance in prescribing drugs for pain relief. We have become increasingly satisfied with the concept of administering analgesics on a scheduled rather thanpro re natabasis in our pain patients and believe there are several advantages... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Pain Rehabilitation Center, S. C. La Crosse, Wisconsin PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1973Volume 79, Issue 6Page: 913-914KeywordsAnalgesicsDrugsInpatients Issue Published: 1 December 1973 PDF downloadLoading ...
Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy
Authors: Carolyn Y. Ho, Matthew E. Mealiffe, Richard G. Bach, Mondira Bhattacharya, Lubna Choudhury, Jay M. Edelberg, Sheila M. Hegde, Daniel Jacoby, Neal K. Lakdawala, Steven J. Lester, Yanfei Ma, Ali J. Marian, Sherif F. Nagueh, Anjali Owens, Florian Rader, Sara Saberi, Amy J. Sehnert, Mark V. Sherrid, Scott D. Solomon, Andrew Wang, Omar Wever-Pinzon, Timothy C. Wong, Stephen B. Heitner
Journal: Journal of the American College of Cardiology (2020)

Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile mechanics of the cardiomyocyte, myosin inhibitors have the potential to modify pathophysiology and improve symptoms associated with HCM.MAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored the safety and efficacy of mavacamten, a first-in-class reversible inhibitor of cardiac-specific myosin, in nHCM.The MAVERICK-HCM trial was a multicenter, double-blind, placebo-controlled, dose-ranging phase II study in adults with symptomatic nHCM (New York Heart Association functional class II/III), left ventricular ejection fraction (LVEF) ≥55%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml. Participants were randomized 1:1:1 to mavacamten at a pharmacokinetic-adjusted dose (targeting plasma levels of 200 or 500 ng/ml), or placebo for 16 weeks, followed by an 8-week washout. Initial dose was 5 mg daily with 1 dose titration at week 6.Fifty-nine participants were randomized (19, 21, 19 patients to 200 ng/ml, 500 ng/ml, placebo, respectively). Their mean age was 54 years, and 58% were women. Serious adverse events occurred in 10% of participants on mavacamten and in 21% participants on placebo. Five participants on mavacamten had reversible reduction in LVEF ≤45%. NT-proBNP geometric mean decreased by 53% in the pooled mavacamten group versus 1% in the placebo group, with geometric mean differences of -435 and -6 pg/ml, respectively (p = 0.0005). Cardiac troponin I (cTnI) geometric mean decreased by 34% in the pooled mavacamten group versus a 4% increase in the placebo group, with geometric mean differences of -0.008 and 0.001 ng/ml, respectively (p = 0.009).Mavacamten, a novel myosin inhibitor, was well tolerated in most subjects with symptomatic nHCM. Furthermore, treatment was associated with a significant reduction in NT-proBNP and cTnI, suggesting improvement in myocardial wall stress. These results set the stage for future studies of mavacamten in this patient population using clinical parameters, including LVEF, to guide dosing. (A Phase 2 Study of Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy [MAVERICK-HCM]; NCT03442764).
メタドキシンは、アルコール患者の脂肪肝の回復を加速する:ランダム化二重盲検プラセボ対照試験の結果 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Caballeria J, Pares A, Bru C, Mercader J, Plaza A G, Caballeria L, Clemente G, Rodrigo L, Rodes J
Journal: Journal of Hepatology (1998)
Chromatin topology reorganization and transcription repression by PML-RARα in acute promyeloid leukemia
Authors: Ping Wang, Zhonghui Tang, Byoungkoo Lee, Jacqueline Jufen Zhu, Liuyang Cai, Przemyslaw Szalaj, Simon Zhongyuan Tian, Meizhen Zheng, Dariusz Plewczynski, Xiaoan Ruan, Edison T. Liu, Chia-Lin Wei, Yijun Ruan
Journal: Genome biology (2020)

Abstract Background Acute promyeloid leukemia (APL) is characterized by the oncogenic fusion protein PML-RARα, a major etiological agent in APL. However, the molecular mechanisms underlying the role of PML-RARα in leukemogenesis remain largely unknown. Results Using an inducible system, we comprehensively analyze the 3D genome organization in myeloid cells and its reorganization after PML-RARα induction and perform additional analyses in patient-derived APL cells with native PML-RARα. We discover that PML-RARα mediates extensive chromatin interactions genome-wide. Globally, it redefines the chromatin topology of the myeloid genome toward a more condensed configuration in APL cells; locally, it intrudes RNAPII-associated interaction domains, interrupts myeloid-specific transcription factors binding at enhancers and super-enhancers, and leads to transcriptional repression of genes critical for myeloid differentiation and maturation. Conclusions Our results not only provide novel topological insights for the roles of PML-RARα in transforming myeloid cells into leukemia cells, but further uncover a topological framework of a molecular mechanism for oncogenic fusion proteins in cancers.
Exploring the “Big HIT” variant of cascade affinity chromatography (CAC) for the purification of prostate specific antigen (PSA)
Authors: Christopher M. Hessick, Eugene Sulkowski, Thamarapu Srikrishnan
Journal: Cancer Research (2006)

1304  Prostate-specific antigen (PSA), a member of the kallikrein family of proteins, is a 30 kDa serine protease produced by the epithelium of the human prostate gland and secreted into seminal fluid. The concentration of PSA in the blood is used as a unique serum biomarker for the early detection of prostate cancer. Chromatography is a very powerful technique that is used to separate and purify biomolecules. Combination of chromatographic techniques termed “Cascade Affinity Cromatography” [CAC] paves the way for an efficient purification. We report here the big “HIT” variant of CAC for the purification of PSA. i) Heparin-Sepharose ii) IMAC (Immobilized Metal-ion Affinity Chromatography) & iii) TIC (Thiophilic Interaction Chromatography). Heparin-Sepharose® requires the presence, clustering, and exposure of basic residues, lysine and arginine, to generate an affinity of a protein. PSA and other kallikreins fulfill these requirements. Our results show that PSA and other kallikreins bind avidly to Heparin-Sepharose® gel. In addition, coupling Heparin-Sepharose® chromatography with immobilized metal-ion affinity chromatography (IMAC) allows further purification of PSA from biological samples. IMAC utilizes binding of histidine residues to transition metals ions chelated to immobilized iminodiacetic acid (IDA). PSA has several histidine residues on its surface as revealed by the tertiary structure of mouse and horse kallikreins. Our preliminary results show that PSA and other kallikreins bind to IDA-Ni2+. TIC utilizes the interaction of thiophilic ligands with aromatic residues exposed on a protein surface. Already, TIC has been successfully applied to separate PSA from its complexes with a variety of inhibitors. Isolation of the protein by TIC has used 2S and 3S gels. Our preliminary results show that purification of PSA is feasible in “HIT”. These investigations led us to develop protocols for the isolation, separation and purification of PSA from its inhibitors such as macroglobulins, anti-chymotrypsin, antitrypsin and their complexes with PSA. In conclusion, Heparin-Sepharose®, IMAC and TIC can be used as cascade affinity chromatography to further purify PSA from biological fluids [HIT of PSA].