tbuckley/cabot-search huggingface dataset:
Deep-learning-based real-time prediction of acute kidney injury outperforms human predictive performance
Authors: Nina Rank, Boris Pfahringer, Jörg Kempfert, Christof Stamm, Titus Kühne, Felix Schoenrath, Volkmar Falk, Carsten Eickhoff, Alexander Meyer
Journal: npj Digital Medicine (2020)

Abstract Acute kidney injury (AKI) is a major complication after cardiothoracic surgery. Early prediction of AKI could prompt preventive measures, but is challenging in the clinical routine. One important reason is that the amount of postoperative data is too massive and too high-dimensional to be effectively processed by the human operator. We therefore sought to develop a deep-learning-based algorithm that is able to predict postoperative AKI prior to the onset of symptoms and complications. Based on 96 routinely collected parameters we built a recurrent neural network (RNN) for real-time prediction of AKI after cardiothoracic surgery. From the data of 15,564 admissions we constructed a balanced training set (2224 admissions) for the development of the RNN. The model was then evaluated on an independent test set (350 admissions) and yielded an area under curve (AUC) (95% confidence interval) of 0.893 (0.862–0.924). We compared the performance of our model against that of experienced clinicians. The RNN significantly outperformed clinicians (AUC = 0.901 vs. 0.745, p &lt; 0.001) and was overall well calibrated. This was not the case for the physicians, who systematically underestimated the risk ( p &lt; 0.001). In conclusion, the RNN was superior to physicians in the prediction of AKI after cardiothoracic surgery. It could potentially be integrated into hospitals’ electronic health records for real-time patient monitoring and may help to detect early AKI and hence modify the treatment in perioperative care.
The Combination of High Total Metabolic Tumor Volume and Poor ECOG Performance Status Defines Ultra-High Risk Diffuse Large B-Cell Lymphoma. Validation across Multiple Cohorts of Large Clinical Trials and in Real World
Authors: Catherine Thieblemont, Loïc Chartier, Ulrich Dührsen, Umberto Vitolo, Sally F Barrington, Laetitia Vercellino, Jan Zaucha, Inês Patrocinio Carvalho, Gomes da Silva Maria, Pierre Decazes, Pierre-Julien Viailly, Herve Tilly, Alina Berriolo-Riedinger, Rene-Olivier Casasnovas, Andreas Hüttmann, Hajira Ilyas, George Mikhaeel, Joel Dunn, Anne Ségolène Cottereau, Christine Schmitz, Joseph N. Paulson, Tina G Nielsen, Michel Meignan
Journal: Blood (2020)
AZA + Glutaminase Inhibition with Telaglenastat (CB-839) for Advanced MDS: An Updated Interim Analysis
Authors: Kapil Saxena, Marina Konopleva, Tushar D Bhagat, Veronica A Guerra, Rita Maduike, Stefano Tiziani, Gautam Borthakur, Elias Jabbour, Naveen Pemmaraju, Tapan M. Kadia, Nicholas J. Short, Jan A. Burger, Steven M. Kornblau, Naval Daver, Kiran Naqvi, Tianyu Cai, Vinitha Mary Kuruvilla, Hagop M. Kantarjian, Guillermo Garcia-Manero, Amit Verma, Courtney D. DiNardo
Journal: Blood (2020)
Imatinib (IM) in Combination with Hydroxyurea Showed Significantly Lower Major Molecular Response Rates at 6 Months but Similar MMR at 18 Months in Patients with CML1st CP Compared to IM Alone. Final Results of the CML2004 Study. NCT 02480608
Authors: Thoralf Lange, Rainer Krahl, Ulrich von Grünhagen, Haifa Kathrin Al-Ali, Schwarzer Andreas, Kathleen Jentsch-Ulrich, Claudia Spohn, Volker Lakner, Michael Assmann, Christian Junghanss, Markus Pfirrmann, Arthur Gil, Rüdiger Hehlmann, Michael W. Deininger, Dietger Niederwieser
Journal: Blood (2017)
tRNA-derived fragments: Mechanisms underlying their regulation of gene expression and potential applications as therapeutic targets in cancers and virus infections
Authors: Xiuchong Yu, Yaoyao Xie, Shuangshuang Zhang, Xuemei Song, Bingxiu Xiao, Zhilong Yan
Journal: Theranostics (2020)

tRNA-derived fragments (tRFs) are a new category of regulatory noncoding RNAs with distinct biological functions in cancers and stress-induced diseases. Herein, we first summarize the classification and biogenesis of tRFs. tRFs are produced from pre-tRNAs or mature tRNAs. Based on the incision loci, tRFs are classified into several types: tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF. Some tRFs participate in posttranscriptional regulation through microRNA-like actions or by displacing RNA binding proteins and regulating protein translation by promoting ribosome biogenesis or interfering with translation initiation. Other tRFs prevent cell apoptosis by binding to cytochrome c or promoting virus replication. More importantly, the dysregulation of tRFs has important clinical implications. They are potential diagnostic and prognostic biomarkers of gastric cancer, liver cancer, breast cancer, prostate cancer, and chronic lymphocytic leukemia. tRFs may become new therapeutic targets for the treatment of diseases such as hepatocellular carcinoma and respiratory syncytial virus infection. Finally, we point out the existing problems and future research directions associated with tRFs. In conclusion, the current progress in the research of tRFs reveals that they have important clinical implications and may constitute novel molecular therapeutic targets for modulating pathological processes.
Enhanced neprilysin-mediated degradation of hippocampal Aβ42 with a somatostatin peptide that enters the brain
Authors: Fadi Rofo, Canan Ugur Yilmaz, Nicole Metzendorf, Tobias Gustavsson, Chiara Beretta, Anna Erlandsson, Dag Sehlin, Stina Syvänen, Per Nilsson, Greta Hultqvist
Journal: Theranostics (2020)

Background: Aggregation of the amyloid-beta (Aβ) peptide is one of the main neuropathological events in Alzheimer's disease (AD).Neprilysin is the major enzyme degrading Aβ, with its activity enhanced by the neuropeptide somatostatin (SST).SST levels are decreased in the brains of AD patients.The poor delivery of SST over the blood-brain barrier (BBB) and its extremely short half-life of only 3 min limit its therapeutic significance.Methods: We recombinantly fused SST to a BBB transporter binding to the transferrin receptor.Using primary neuronal cultures and neuroblastoma cell lines, the ability of the formed fusion protein to activate neprilysin was studied.SST-scFv8D3 was administered to mice overexpressing the Aβ-precursor protein (AβPP) with the Swedish mutation (APPswe) as a single injection or as a course of three injections over a 72 h period.Levels of neprilysin and Aβ were quantified using an Enzyme-linked immunosorbent assay (ELISA).Distribution of SST-scFv8D3 in the brain, blood and peripheral organs was studied by radiolabeling with iodine-125.Results: The construct, SST-scFv8D3, exhibited 120 times longer half-life than SST alone, reached the brain in high amounts when injected intravenously and significantly increased the brain concentration of neprilysin in APPswe mice.A significant decrease in the levels of membrane-bound Aβ42 was detected in the hippocampus and the adjacent cortical area after only three injections. Conclusion:With intravenous injections of our BBB permeable SST peptide, we were able to significantly increase the levels neprilysin, an effect that was followed by a significant and selective degradation of membrane-bound Aβ42 in the hippocampus.Being that membrane-bound Aβ triggers neuronal toxicity and the hippocampus is the central brain area in the progression of AD, the study has illuminated a new potential treatment paradigm with a promising safety profile targeting only the disease affected areas.
Proposed Additions to the NCCN Guidelines for Adult Medulloblastoma
Authors: Marta Penas-Prado, Terri S. Armstrong, Mark R. Gilbert
Journal: Journal of the National Comprehensive Cancer Network (2020)

Medulloblastoma is a rare brain tumor that occurs in both children and adults, with patients aged 15 to 39 years accounting for 30% of all cases. In adults, guidelines for diagnosis and treatment are often based on retrospective data and extrapolated from the pediatric experience due to limited availability of prospective trials or registries involving adults. Importantly, adult patients differ from pediatric patients in many aspects, including the molecular features of the tumor and tolerance to treatment. In 2017, the NCI was granted support from the Cancer Moonshot initiative to address the challenges and unmet needs of adults with rare central nervous system (CNS) tumors through the NCI Comprehensive Oncology Network for Evaluating Rare CNS Tumors (NCI-CONNECT). On November 25, 2019, NCI-CONNECT convened a multidisciplinary workshop on adult medulloblastoma. Working groups identified unmet needs in clinical care and research and developed specific action items, including a proposal for inclusion of new items in the NCCN Guidelines for Adult Medulloblastoma, delineated in this review along with the evidence supporting their incorporation. Recommendations included facilitating referral of patients to centers of excellence; promoting patient participation in clinical trials or registries; encouraging use of DNA methylation for confirmation of diagnosis and subgrouping; offering counseling on contraception and fertility preservation; evaluating patients for symptoms and medical management of endocrine, vision, hearing, and neurocognitive deficits; providing psychosocial support and referral to neurorehabilitation; minimizing delays in therapy; and incorporating imaging standards and criteria for progression.
Efficacy of Daratumumab Containing Regimens Post Lenalidomide Maintenance in Transplant Eligible Patients: Real-World Experience from the Canadian Myeloma Research Group Database
Authors: Hira S Mian, Christine Eisfeld, Christopher P. Venner, Victor Jimenez-Zepeda, Cyrus Khandanpour, Arleigh McCurdy, Michael Sebag, Kevin W Song, Richard Leblanc, Esther Masih-Khan, Eshetu G Atenafu, Darrell J White, Julie Stakiw, Anthony Reiman, Martha L Louzada, Muhammad Aslam, Rami Kotb, Engin Gul, Donna E. Reece
Journal: Blood (2020)
Brain exposure of the ATM inhibitor AZD1390 in humans—a positron emission tomography study
Authors: Aurelija Jucaite, Per Stenkrona, Zsolt Cselényi, Serena De Vita, Nuria Buil-Bruna, Katarina Varnäs, Alicia Savage, Andrea Varrone, Peter Johnström, Magnus Schou, Chris Davison, Andy Sykes, Venkatesh Pilla Reddy, Matthias Hoch, Ana Vazquez-Romero, Mohammad Mahdi Moein, Christer Halldin, Melinda S Merchant, Martin Pass, Lars Farde
Journal: Neuro-Oncology (2020)

The protein kinase ataxia telangiectasia mutated (ATM) mediates cellular response to DNA damage induced by radiation. ATM inhibition decreases DNA damage repair in tumor cells and affects tumor growth. AZD1390 is a novel, highly potent, selective ATM inhibitor designed to cross the blood-brain barrier (BBB) and currently evaluated with radiotherapy in a phase I study in patients with brain malignancies. In the present study, PET was used to measure brain exposure of 11C-labeled AZD1390 after intravenous (i.v.) bolus administration in healthy subjects with an intact BBB.AZD1390 was radiolabeled with carbon-11 and a microdose (mean injected mass 1.21 µg) was injected in 8 male subjects (21-65 y). The radioactivity concentration of [11C]AZD1390 in brain was measured using a high-resolution PET system. Radioactivity in arterial blood was measured to obtain a metabolite corrected arterial input function for quantitative image analysis. Participants were monitored by laboratory examinations, vital signs, electrocardiogram, adverse events.The brain radioactivity concentration of [11C]AZD1390 was 0.64 SUV (standard uptake value) and reached maximum 1.00% of injected dose at Tmax[brain] of 21 min (time of maximum brain radioactivity concentration) after i.v. injection. The whole brain total distribution volume was 5.20 mL*cm-3. No adverse events related to [11C]AZD1390 were reported.This study demonstrates that [11C]AZD1390 crosses the intact BBB and supports development of AZD1390 for the treatment of glioblastoma multiforme or other brain malignancies. Moreover, it illustrates the potential of PET microdosing in predicting and guiding dose range and schedule for subsequent clinical studies.
Alginate and alginate composites for biomedical applications
Authors: Raha Ahmad Raus, Wan Mohd Fazli Wan Nawawi, Ricca Rahman Nasaruddin
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Alginate is an edible heteropolysaccharide that abundantly available in the brown seaweed and the capsule of bacteria such as Azotobacter sp. and Pseudomonas sp. Owing to alginate gel forming capability, it is widely used in food, textile and paper industries; and to a lesser extent in biomedical applications as biomaterial to promote wound healing and tissue regeneration. This is evident from the rising use of alginate-based dressing for heavily exuding wound and their mass availability in the market nowadays. However, alginate also has limitation. When in contact with physiological environment, alginate could gelate into softer structure, consequently limits its potential in the soft tissue regeneration and becomes inappropriate for the usage related to load bearing body parts. To cater this problem, wide range of materials have been added to alginate structure, producing sturdy composite materials. For instance, the incorporation of adhesive peptide and natural polymer or synthetic polymer to alginate moieties creates an improved composite material, which not only possesses better mechanical properties compared to native alginate, but also grants additional healing capability and promote better tissue regeneration. In addition, drug release kinetic and cell viability can be further improved when alginate composite is used as encapsulating agent. In this review, preparation of alginate and alginate composite in various forms (fibre, bead, hydrogel, and 3D-printed matrices) used for biomedical application is described first, followed by the discussion of latest trend related to alginate composite utilization in wound dressing, drug delivery, and tissue engineering applications.
Ex-Vivo FT-4202 Treatment Improves Hemoglobin Oxygen Affinity and Membrane Health in Red Blood Cells of Patients with Hemoglobin SS and Hemoglobin SC Disease Irrespective of Prior Hydroxyurea Use
Authors: Diamantis G. Konstantinidis, Rose Fessler, Katie Giger Seu, Bhargav Patel, Jennifer B Korpik, Keertik Fulzele, Sylvie Guichard, Theodosia A. Kalfa
Journal: Blood (2020)
Training: BMA expresses concern over changes to specialty recruitment
Authors: Abi Rimmer
Journal: BMJ (2020)

Recruitment for specialty training has been substantially changed this year, with all interviews taking place online and an increased use of computer based testing. The BMA has raised concerns about the changes that affect the 2021 recruitment round for specialty training across the UK.1

In a webinar on 21 October Health Education England set out the changes that will be introduced owing to the covid-19 pandemic.2 There will be increased reliance on the computer based multispecialty recruitment assessment (MSRA). Although this test is already used by some specialties, such as general practice, applicants to acute care common stem and paediatrics will need to take this test for the first time this year.

All interviews will take place online, and there will be no interviews at all for applicants to general practice and psychiatry. Appointments to …
A Prospective, Multicenter Study of Bortezomib, Cyclophosphamide and Dexamethasone in Relapsed/Refractory Idiopathic Multicentric Castleman's Disease
Authors: Lu Zhang, Ming-nan Jia, Ai-lin Zhao, Jun Feng, Xin-xin Cao, Yan Zhang, Ming-hui Duan, Dao-Bin Zhou, Yujun Dong, Jian Li
Journal: Blood (2020)
A Novel Therapeutic DNA Vaccine Elicits Reduction of Tumor Clones and Favorable Perturbations in the Immune Microenvironment in Patients (pts) with Untreated Smoldering Waldenström Macroglobulinemia (sWM)
Authors: Sheeba K. Thomas, Soung-chul Cha, Sapna R Parshottam, Sheetal S. Rao, Jasper B. Olsem, Brandon N. Crumpton, Szymon Szymura, Zhe Wang, Aaron Anderson, Lei Feng, Hans C. Lee, Elisabet E. Manasanch, Krina K. Patel, Donna M. Weber, Robert Z. Orlowski, Sattva S. Neelapu, Larry W Kwak
Journal: Blood (2020)
Biomarker Driven Umbrella Trial of Crenolanib in Combination with Ivosidenib, Enasidenib, Venetoclax, Vyxeos and/or Salvage Chemotherapy in FLT3 Mutant AML
Authors: Naval Daver, Aaron D Goldberg, Courtney D. DiNardo, Tapan M. Kadia, Eunice S. Wang, Richard M. Stone, Han Zhang, Boo Messahel
Journal: Blood (2020)
Heterogeneity of Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma
Authors: Ivana Spasevska, Sarah Josefsson, Yngvild Nuvin Blaker, Chloe B. Steen, Ankush Sharma, Kushi Kushekhar, Saskia Meyer, Arne Kolstad, Klaus Beiske, Harald Holte, Bjørn Østenstad, Eva Kimby, Johanna Olweus, Kjetil Tasken, Suzanne Lorenz, Erlend B. Smeland, Ash A. Alizadeh, Kanutte Huse, June Helen Myklebust
Journal: Blood (2020)
A New Risk Stratification Model (R2-ISS) in Newly Diagnosed Multiple Myeloma: Analysis of Mature Data from 7077 Patients Collected By European Myeloma Network within Harmony Big Data Platform
Authors: Mattia D'Agostino, Juan-José Lahuerta, Ruth Wester, Anders Waage, Uta Bertsch, Elena Zamagni, Maria-Victoria Mateos, Alessandra Larocca, Daniele Dall'Olio, Niels W. C. J. van de Donk, David Cairns, Serena Rocchi, Hans Salwender, Joan Blade Creixenti, Bronno van der Holt, Castellani Gastone, Giovannino Ciccone, Andrea Capra, Jan Dürig, Sara Bringhen, Sonja Zweegman, Michele Cavo, Hartmut Goldschmidt, Gordon Cook, Jesus Maria Hernández-Rivas, Jesus F. San-Miguel, Mario Boccadoro, Pieter Sonneveld
Journal: Blood (2020)
Diagnosing asthma in children or adolescents/young adults? It is time for a change! How timing is everything, also in clinical practice
Authors: Peter J. Merkus, Mariëlle W. Pijnenburg
Journal: European Respiratory Journal (2020)

In 1190 AD, in one of the first expert-based guidelines on asthma, Maimonides already points out that "asthma should be treated according to the various causes that bring it about." He further states that "one can only manage the disease properly with a thorough knowledge of the patient's constitution and his individual organs, his age and habits, the season and the climate" [1]. So he already recognised several risk factors, such as genetic components, environmental exposures and comorbidities. Since then, we have come a long way, and think we understand and treat asthma better, but we can still struggle to diagnose or rule out asthma in patients who are referred to us. And this is even more of a challenge when we are dealing with (young) children. It is time to innovate the way we look at (diagnosing) asthma <https://bit.ly/38SKy1C>
Global and regional epidemiology of HIV-1 recombinants in 1990–2015: a systematic review and global survey
Authors: Joris Hemelaar, Ramyiadarsini Elangovan, Jason Yun, Leslie Dickson-Tetteh, Shona Kirtley, Eleanor Gouws-Williams, Peter D Ghys, Alash'le G Abimiku, Simon Agwale, Chris Archibald, Boaz Avidor, María Gabriela Barbás, Francoise Barre-Sinoussi, Banson Barugahare, El Hadj Belabbes, Silvia Bertagnolio, Deborah Birx, Aleksei F Bobkov, James Brandful, Helba Bredell, Catherine A Brennan, James Brooks, Marie Bruckova, Luigi Buonaguro, Franco Buonaguro, Stefano Buttò, Anne Buvé, Mary Campbell, Jean Carr, Alex Carrera, Manuel Gómez Carrillo, Connie Celum, Beth Chaplin, Macarthur Charles, Dimitrios Chatzidimitriou, Zhiwei Chen, Katsumi Chijiwa, David Cooper, Philip Cunningham, Anoumou Dagnra, Cillian F de Gascun, Julia Del Amo, Elena Delgado, Ursula Dietrich, Dominic Dwyer, Dennis Ellenberger, Barbara Ensoli, Max Essex, Feng Gao, Hervé Fleury, Peter N Fonjungo, Vincent Foulongne, Deepak A Gadkari, Feng Gao, Federico García, Roger Garsia, Guy Michel Gershy-Damet, Judith R Glynn, Ruth Goodall, Zehava Grossman, Monick Lindenmeyer-Guimarães, Beatrice Hahn, Raph L Hamers, Osamah Hamouda, Ray Handema, Xiang He, Joshua Herbeck, David D Ho, Africa Holguin, Mina Hosseinipour, Gillian Hunt, Masahiko Ito, Mohamed Ali Bel Hadj Kacem, Erin Kahle, Pontiano Kaleebu, Marcia Kalish, Adeeba Kamarulzaman, Chun Kang, Phyllis Kanki, Edward Karamov, Jean-Claude Karasi, Kayitesi Kayitenkore, Tony Kelleher, Dwip Kitayaporn, Leondios G Kostrikis, Claudia Kucherer, Claudia Lara, Thomas Leitner, Kirsi Liitsola, Jai Lingappa, Marek Linka, Ivette Lorenzana de Rivera, Vladimir Lukashov, Shlomo Maayan, Luzia Mayr, Francine McCutchan, Nicolas Meda, Elisabeth Menu, Fred Mhalu, Doreen Mloka, John L Mokili, Brigitte Montes, Orna Mor, Mariza Morgado, Fausta Mosha, Awatef Moussi, James Mullins, Rafael Najera, Mejda Nasr, Nicaise Ndembi, Joel R Neilson, Vivek R Nerurkar, Florian Neuhann, Claudine Nolte, Vlad Novitsky, Philippe Nyambi, Marianna Ofner, Fem J Paladin, Anna Papa, Jean Pape, Neil Parkin, Chris Parry, Martine Peeters, Alexandra Pelletier, Lucía Pérez-Álvarez, Deenan Pillay, Angie Pinto, Trinh Duy Quang, Cecilia Rademeyer, Filimone Raikanikoda, Mark A Rayfield, Jean-Marc Reynes, Tobias Rinke de Wit, Kenneth E Robbins, Morgane Rolland, Christine Rousseau, Jesus Salazar-Gonzales, Hanan Salem, Mika Salminen, Horacio Salomon, Paul Sandstrom, Mario L Santiago, Abdoulaye D Sarr, Bryan Schroeder, Michel Segondy, Philippe Selhorst, Sylvester Sempala, Jean Servais, Ansari Shaik, Yiming Shao, Amine Slim, Marcelo A Soares, Elijah Songok, Debbie Stewart, Julie Stokes, Shambavi Subbarao, Ruengpung Sutthent, Jun Takehisa, Amilcar Tanuri, Kok Keng Tee, Kiran Thapa, Michael Thomson, Tyna Tran, Willy Urassa, Hiroshi Ushijima, Philippe van de Perre, Guido van der Groen, Kristel van Laethem, Joep van Oosterhout, Ard van Sighem, Eric van Wijngaerden, Anne-Mieke Vandamme, Jurgen Vercauteren, Nicole Vidal, Lesley Wallace, Carolyn Williamson, Dawit Wolday, Jianqing Xu, Chunfu Yang, Linqi Zhang, Rong Zhang
Journal: The Lancet HIV (2020)
Abstract 331: Impact of Acetylated Cyclophilin D on the Mitochondrial Permeability Transition Pore
Authors: Gisela Beutner, Jacob Perkins, Ronak A Sardari, George A Porter
Journal: Circulation Research (2020)

Background: The mitochondrial matrix protein cyclophilin D (CypD) is a key regulator of mitochondrial function. CypD controls electron transport chain activity and ATP synthesis by regulating the permeability transition pore (PTP). The activity of CypD is regulated by several post-translational modifications including acetylation of lysine 166 in the mouse. Objective: To investigate how acetylation at lysine 166 of CypD specifically in the heart modifies its ability to regulate the PTP and the ATP synthase. Results: We generated a conditional cardiac knock-in mouse model where lysine 166 has been mutated into glutamine (CypD K166Q ) to mimic permanent acetylation of CypD. The mice were either +/+, +/- or -/- for the expression of native CypD. Results show that mitochondrial oxygen consumption was not affected by the expression of CypD K166Q . The calcium retention capacity (CRC) was measured with Arsenazo III and decreased significantly when CypD K166Q was expressed. The CypD inhibitor cyclosporine A significantly increased the CRC in WT mice. However, cyclosporine A was did not inhibit CypD in the hearts of mice expressing only CypD K166Q or in addition to wild-type CypD. The ability of the ATP synthase to create dimers or oligomers was assessed by western blotting and the hydrolysis of ATP in in-gel assays and shows that expression of CypD K166Q decreased the assembly of the ATP synthase into dimers or oligomers. Conclusions: Our data show that the expression of CypD K166Q increases the sensitivity of PTP opening to calcium and limits the assembly of ATP synthase into oligomers.