tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Ublituximab in Combination with Umbralisib (U2) in Patients with Chronic Lymphocytic Leukemia (CLL) By Treatment Status: A Sub-Analysis of the Phase 3 Unity-CLL Study
Authors: Ryan Jacobs, Wojciech Jurczak, Ian W. Flinn, Sebastian Grosicki, Krzysztof Giannopoulos, Tomasz Wróbel, Syed F. Zafar, Jennifer L. Cultrera, Suman Kambhampati, Alexey V. Danilov, John M. Burke, Jerome Goldschmidt, Douglas F. Beach, Scott F. Huntington, Javier Pinilla Ibarz, Jeff P. Sharman, Tanya Siddiqi, Danielle M. Brander, Mazyar Shadman, John M. Pagel, Monika Dlugosz-Danecka, Nilanjan Ghosh, Kathryn S. Kolibaba, Peter Sportelli, Hari P. Miskin, Owen A. O'Connor, Michael S. Weiss, John G. Gribben
Journal: Blood (2021)
Nano-scale physical properties characteristic to metastatic intestinal cancer cells identified by high-speed scanning ion conductance microscope
Authors: Dong Wang, Linhao Sun, Satoru Okuda, Daisuke Yamamoto, Mizuho Nakayama, Hiroko Oshima, Hideyuki Saito, Yuta Kouyama, Koshi Mimori, Toshio Ando, Shinji Watanabe, Masanobu Oshima
Journal: Biomaterials (2021)

Recent genetic studies have indicated relationships between gene mutations and colon cancer phenotypes. However, how physical properties of tumor cells are changed by genetic alterations has not been elucidated. We examined genotype-defined mouse intestinal tumor-derived cells using a high-speed scanning ion conductance microscope (HS-SICM) that can obtain high-resolution live images of nano-scale topography and stiffness. The tumor cells used in this study carried mutations in Apc (A), Kras (K), Tgfbr2 (T), Trp53 (P), and Fbxw7 (F) in various combinations. Notably, high-metastatic cancer-derived cells carrying AKT mutations (AKT, AKTP, and AKTPF) showed specific ridge-like morphology with active membrane volume change, which was not found in low-metastatic and adenoma-derived cells. Furthermore, the membrane was significantly softer in the metastatic AKT-type cancer cells than other genotype cells. Importantly, a principal component analysis using RNAseq data showed similar distributions of expression profiles and physical properties, indicating a link between genetic alterations and physical properties. Finally, the malignant cell-specific physical properties were confirmed by an HS-SICM using human colon cancer-derived cells. These results indicate that the HS-SICM analysis is useful as a novel diagnostic strategy for predicting the metastatic ability of cancer cells.
Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial
Authors: Raches Ella, Siddarth Reddy, William Blackwelder, Varsha Potdar, Pragya Yadav, Vamshi Sarangi, Vinay K Aileni, Suman Kanungo, Sanjay Rai, Prabhakar Reddy, Savita Verma, Chandramani Singh, Sagar Redkar, Satyajit Mohapatra, Anil Pandey, Pajanivel Ranganadin, Raghavendra Gumashta, Manish Multani, Shameem Mohammad, Parul Bhatt, Laxmi Kumari, Gajanan Sapkal, Nivedita Gupta, Priya Abraham, Samiran Panda, Sai Prasad, Balram Bhargava, Krishna Ella, Krishna Mohan Vadrevu, P. Aggarwal, V. Aglawe, A. Ali, N. Anand, N. Awad, V. Bafna, G. Balasubramaniyam, A. Bandkar, P. Basha, V. Bharge, A. Bhate, S. Bhate, V. Bhavani, R. Bhosale, DV Chalapathy, C. Chaubal, D. Chaudhary, A. Chavan, P. Desai, D. Dhodi, S. Dutta, R. Garg, K. Garg, M. George, P. Goyal, R. Guleria, S. Gupta, M. Jain, M.K. Jain, S. Jindal, M. Kalra, S. Kant, P. Khosla, P. Kulkarni, P. Kumar, Y. Kumar, A. Majumdar, P. Meshram, V. Mishra, S. Mohanty, J. Nair, S. Pandey, S.K. Panigrahi, B. Patil, V. Patil, P. Rahate, V. Raj, S. Ramanand, K. Rami, B. Ramraj, S. Rane, E.V. Rao, N. Rao, R. Raphael, G. Reddy, V. Redkar, S. Redkar, A. Sachdeva, J. Saha, J. Sahoo, P. Sampath, A. Savith, M. Shah, L. Shanmugam, R. Sharma, P. Sharma, D. Sharma, A. Singh, J. Singh, P. Singh, S. Sivaprakasam, S. Subramaniam, D. Sudheer, S. Tandon, M. Tariq, V. Tripathi, M. Vable, R. Verma, S. Waghmare
Journal: The Lancet (2021)
Prognostic Impact of <i>MYD88</i> L265P Mutation By Droplet Digital PCR in IgM MGUS and Smoldering Waldenström Macroglobulinemia
Authors: David F. Moreno, Sara Paz, Mari-Pau Mena, Monica Lopez-Guerra, Aina Oliver-Caldes, Anthony M Battram, Luis Gerardo Rodríguez-Lobato, Natalia Tovar, M. Teresa Cibeira, Raquel Jiménez-Segura, Joan Bladé Creixenti, Laura Rosinol, Dolors Colomer, Carlos Fernandez de Larrea
Journal: Blood (2021)
Prognostic Value of Measurable Residual Disease Assessed By Multiparameter Flowcytometry in Patients with NPM1-Mutated Acute Myeloid Leukemia
Authors: Sangeetha Venugopal, Nicholas J. Short, Jeffrey L. Jorgensen, Tapan M. Kadia, Courtney D. DiNardo, Marina Konopleva, Sherry A. Pierce, Sanam Loghavi, Keyur P. Patel, Ghayas C. Issa, Hagop Kantarjian, Sa A Wang, Farhad Ravandi
Journal: Blood (2021)
Physician vacancies are at highest level in almost a decade, colleges find
Authors: Abi Rimmer
Journal: BMJ (2021)

The proportion of unfilled consultant physician posts across the UK is at its highest level in almost a decade, medical royal colleges have warned.

A census conducted by the Royal College of Physicians, the Royal College of Physicians of Edinburgh, and the Royal College of Physicians and Surgeons of Glasgow found that nearly half (48%, 855) of advertised consultant posts across the UK were unfilled last year, up from 36% in 2013.

Of the posts that went unfilled in the UK, almost half (49%, 419) were …
Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures
Authors: John Crawford, Jeffrey Gold, Richard Haas
Journal: JAMA Neurology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Breast Implant Associated-Anaplastic Large-Cell Lymphoma (BIA-ALCL): Data Based on the Lymphoma Study Association (LYSA) Registry. Promising Results of Brentuximab Vedotin Combined with Cyclophosphamide, Doxorubicin and Prednisone (BV-CHP) As First Line Treatment for Patient Requiring Chemotherapy
Authors: Fabien Le Bras, Jean Marc Schiano De Colella, Lucie Oberic, Emmanuel Itti, Thua-Ha Dao, Camille Laurent, Luc Xerri, Emmanuel Bachy, Alexandra Traverse-Glehen, Christophe Bonnet, Marc André, Luc Mathieu Fornecker, Marie Bannier, Bohrane Slama, Youlia Kirova, Emmanuelle Nicolas-Virelizier, Manon Croix, Patrick Fogarty, Nadia Amara, Virginie Fataccioli, Romain Ricci, Hervé Tilly, Lionel Tortolano, Romain Bosc, Philippe Gaulard, Corinne Haioun
Journal: Blood (2021)
A Temporal and Multinational Assessment of Acute Myeloid Leukemia (AML) Cancer Incidence, Survival, and Disease Burden
Authors: Laura J. Anderson, Mariam S. Girguis, Ju-Hyeun Kim, Jitesh B. Shewale, Megan Braunlin, Winifred Werther, Juliana E. Hidalgo-Lopez, Faraz Zaman, Christopher Kim
Journal: Blood (2021)
Temporal convolutional networks predict dynamic oxygen uptake response from wearable sensors across exercise intensities
Authors: Robert Amelard, Eric T. Hedge, Richard L. Hughson
Journal: npj Digital Medicine (2021)

Oxygen consumption ([Formula: see text]) provides established clinical and physiological indicators of cardiorespiratory function and exercise capacity. However, [Formula: see text] monitoring is largely limited to specialized laboratory settings, making its widespread monitoring elusive. Here we investigate temporal prediction of [Formula: see text] from wearable sensors during cycle ergometer exercise using a temporal convolutional network (TCN). Cardiorespiratory signals were acquired from a smart shirt with integrated textile sensors alongside ground-truth [Formula: see text] from a metabolic system on 22 young healthy adults. Participants performed one ramp-incremental and three pseudorandom binary sequence exercise protocols to assess a range of [Formula: see text] dynamics. A TCN model was developed using causal convolutions across an effective history length to model the time-dependent nature of [Formula: see text]. Optimal history length was determined through minimum validation loss across hyperparameter values. The best performing model encoded 218 s history length (TCN-VO2 A), with 187, 97, and 76 s yielding <3% deviation from the optimal validation loss. TCN-VO2 A showed strong prediction accuracy (mean, 95% CI) across all exercise intensities (-22 ml min-1, [-262, 218]), spanning transitions from low-moderate (-23 ml min-1, [-250, 204]), low-high (14 ml min-1, [-252, 280]), ventilatory threshold-high (-49 ml min-1, [-274, 176]), and maximal (-32 ml min-1, [-261, 197]) exercise. Second-by-second classification of physical activity across 16,090 s of predicted [Formula: see text] was able to discern between vigorous, moderate, and light activity with high accuracy (94.1%). This system enables quantitative aerobic activity monitoring in non-laboratory settings, when combined with tidal volume and heart rate reserve calibration, across a range of exercise intensities using wearable sensors for monitoring exercise prescription adherence and personal fitness.
A Phase II Study of 5-Azacytidine (AZA) and Venetoclax As Maintenance Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission
Authors: Alexandre Bazinet, Hagop Kantarjian, Gautam Borthakur, Musa Yilmaz, Prithviraj Bose, Elias J. Jabbour, Yesid Alvarado, Kelly S. Chien, Naveen Pemmaraju, Koichi Takahashi, Nicholas J. Short, Ghayas C. Issa, Nitin Jain, Alessandra Ferrajoli, Jan A. Burger, Debra Bull Linderman, Naval Daver, Courtney D. DiNardo, Marina Konopleva, Guillermo Garcia-Manero, Koji Sasaki, Farhad Ravandi, Tapan M. Kadia
Journal: Blood (2021)
Results from a Phase 2 Study of a Novel Janus Kinase Inhibitor in Treatment of Patients with Myelofibrosis
Authors: Yi Zhang, Hu Zhou, Zhongxing Jiang, DengShu Wu, Junling Zhuang, Wei Li, Qian Jiang, XiuLi Wang, Jinwen Huang, Huan-Ling Zhu, RuiJuan Zhang, Xin Du, Li Fei, Ruixiang Xiang, Feng Zhang, Jianda Hu, Yan Li, Yu Hu, Jing Liu, ChengHao Jin, Kai Sun, Ze-Ping Zhou, Jie Jin
Journal: Blood (2021)
Abstract 8928: Le Coeur En Sabot: Shape and Regional Function Predict Adverse Outcome in Patients with Repaired Tetralogy of Fallot
Authors: Anna Mira, Pablo Lamata, Alistair Young, Thomas Pickardt, Animesh A Tandon, Samir Sarikouch, Jeff Omens, Heiner Latus, Philipp B Beerbaum, Sven Koehler, Malenka Bissell, Zachary Blair, Tyler Huffaker, Kuberan Pushparajah, Charlene Mauger, Georgina Abraham, Andrew McCulloch, Gerald Greil, Sandy Engelhardt, Mohammad Hussain
Journal: Circulation (2021)

Introduction: “Le Coeur en Sabot” (or the boot-shaped heart) is a radiological description of the appearance of the heart on a plain radiograph of a patient with Tetralogy of Fallot. This highlights the importance of the shape of the heart. Maladaptive remodeling is known to occur in patients with repaired Tetralogy of Fallot (rToF) due to residual lesions such as Pulmonary Regurgitant Fraction (PRF) Hypothesis: Shape and function analysis can reveal novel remodeling patterns associated with adverse events in patients with rToF Methods: Biventricular shape and function were studied in 192 patients with rToF (median age 15 years). Linear discriminative analysis (LDA) and principal component analysis (PCA) were used to identify shape differences between patients with and without adverse events (AE). AE included death, arrhythmias, and cardiac arrest (median follow-up 10 years) Results: LDA and PCA showed that shape characteristics pertaining to adverse events included a more circular LV (decreased eccentricity), dilated (increased sphericity) LV base, increased RV apical sphericity, and decreased RV basal sphericity. Multivariate LDA showed that the optimal discriminative model included only RV apical ejection fraction and one PCA mode associated with a more circular and dilated LV base (AUC = 0.78). PRF did not add value, and shape changes associated with increased PRF were not predictive of AE. Conclusions: Remodeling patterns in patients with rToF are associated with AE, independent of PRF. Mechanisms leading to AE include LV basal dilation with a reduced RV apical ejection fraction. That is to say that the old descriptor, “Le Coeur en Sabot'' may also describe that shape that is adverse in rTOF. The toe of this boot would be the dilated and poorly contractile RV apex and the ankle would be the spherical LV base (Figure 1: Top Row Diastole. Middle Systole. Posterior projection (a), anatomical position (b) and superior (c). LV is green)
A Bispecific Antibody Targeting CD117 and CD3 Enables T Cell Mediated Killing of CD117-Expressing Healthy and Malignant Hematopoietic Cells
Authors: Jonathan D Kiefer, Renier Myburgh, Norman F Russkamp, Laura Volta, Adrian Guggisberg, Omar Abdelmotaleb, Jacqueline Mock, Dario Neri, Markus G Manz
Journal: Blood (2021)
Outcomes of Triple Class (Proteasome Inhibitor, IMiDs and Monoclonal Antibody) Refractory Patients with Multiple Myeloma
Authors: Saurabh Zanwar, Matthew Ho, Prashant Kapoor, Angela Dispenzieri, Morie A. Gertz, Martha Q. Lacy, Francis K. Buadi, Suzanne R. Hayman, David Dingli, Taxiarchis Kourelis, Amie Fonder, Yi L. Hwa, Miriam A. Hobbs, Wilson I Gonsalves, Rahma M Warsame, Eli Muchtar, Nelson Leung, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Journal: Blood (2021)
The First-in-Human Clinical Trial of iPSC-Derived Platelets (iPLAT1): Autologous Transfusion to an Aplastic Anemia Patient with Alloimmune Platelet Transfusion Refractoriness
Authors: Naoshi Sugimoto, Junya Kanda, Sou Nakamura, Toshiyuki Kitano, Masakatsu Hishizawa, Tadakazu Kondo, Shin Shimizu, Akiko Shigemasa, Hideyo Hirai, Harue Tada, Manabu Minami, Naohide Watanabe, Masayuki Nogawa, Makoto Handa, Yoshihiko Tani, Akifumi Takaori-Kondo, Koji Eto
Journal: Blood (2021)
Relationship and Susceptibility to Serious Infections Among Monoclonal B-Cell Lymphocytosis (MBL), Monoclonal Gammopathy of Undetermined Significance (MGUS), and Clonal Hematopoiesis (CH) Premalignant Conditions
Authors: Nicholas J. Boddicker, Sameer A. Parikh, Geffen Kleinstern, Aaron D. Norman, Kari G. Rabe, Timothy G. Call, Janet E. Olson, Angela Dispenzieri, David L Murray, S. Vincent Rajkumar, Shaji Kumar, James R. Cerhan, Neil E. Kay, Esteban Braggio, Curtis A. Hanson, Tait Shanafelt, Celine M. Vachon, Susan L. Slager
Journal: Blood (2021)
Abstract 13446: Rapid Eye Movement Sleep is Associated With Ambulatory Blood Pressure in Hypertension
Authors: Soumya Vungarala, sreeja sompalli, Prachi Singh, Alexandria B Danyluk, Fatima H Kuniyoshi, Virend K Somers, Naima Covassin
Journal: Circulation (2021)

Introduction: Growing evidence suggests that aberrant sleep architecture is linked to heightened risk of cardiovascular disease independently of sleep apnea. Rapid Eye Movement (REM) sleep is characterized by increased sympathetic activity and blood pressure (BP) compared to non-REM sleep stages. However, whether REM sleep is associated with BP across the 24 hours has not been investigated. Hypothesis: We hypothesized that increased REM sleep would be associated with higher ambulatory BP. Methods: We recruited 137 individuals (58% men, aged 39±14 years, office systolic/diastolic BP [SBP/DBP] 125±14/77±11 mmHg) who completed overnight polysomnography followed by 24-h ambulatory BP monitoring. Sleep was scored according to standard criteria. 24-h, daytime, and nighttime averages were calculated for SBP, DBP and heart rate. REM sleep duration was computed as percentage of total sleep time and used to group participants into tertiles as follows: T1 (REM% ≤18.8), T2 (REM% 18.9-24), and T3 (REM% ≥24.1). Results: Sex ratio, body mass index, and apnea-hypopnea index were similar across REM tertiles, but age increased with increasing tertiles (p=0.029). 24-h SBP (T1 vs T2 vs T3: 121±12 vs 117±7 vs 124±12 mmHg, p=0.015) and DBP (72±7 vs 70±6 vs 76±8 mmHg, p&lt;0.001) differed across REM sleep tertiles, with significantly higher values in those in the highest tertile. Results were consistent when considering daytime SBP (T1 vs T2 vs T3: 126±12 vs 122±8 vs 132±14 mmHg, p&lt;0.001) and DBP (77±7 vs 76±6 vs 83±9 mmHg, p&lt;0.001), and nighttime DBP (65±9 vs 61±7 vs 65±8 mmHg, p=0.047). No differences were noted on nighttime SBP or any heart rate measures. A significant interaction was found between hypertension status and REM sleep in multiple regression analysis, with the observed associations being significant only among hypertensives (n=69). In those with hypertension, REM sleep duration was associated with 24-h mean BP independently of age, sex, body mass index, apnea-hypopnea index and antihypertensive medications (standardized beta 0.22, p=0.041). Conclusions: Longer REM sleep duration is independently associated with elevated ambulatory BP in individuals with hypertension. REM sleep may be a novel cardiovascular risk indicator in this population.
Platform Incorporating Patient Navigation, Preparative Guidelines, and Hospital at Home May Improve COVID-19 Outcomes for Patients with Myeloid Malignancies
Authors: Brittany Knick Ragon, Tamara K. Moyo, Ashley Sumrall, Ifeyinwa (IFY) Osunkwo, Kris Blackley, Laura Kabrich, Kelly A. Leonard, Ben Masten, Beth York, Stephanie Murphy, Brian Kersten, Thomas Batchelor, Carly Rivet, Armida Parala-Metz, Zainab Shahid, Jean Chai, Laura Musselwhite, Nilay A. Shah, Srinivasa Reddy R. Sanikommu, Aleksander L. Chojecki, Thomas G. Knight, Jing Ai, Belinda R Avalos, Michael R. Grunwald, Edward A. Copelan, Declan Walsh
Journal: Blood (2021)
Can We Lower the Platelet Threshold of ≥50x10 9/L for Performing a Lumbar Puncture Safely in Patients with Hematological Malignancies?
Authors: Aryanna Jordan, Akriti G Jain, Gautam Krishna Koipallil, Meghana Reddy, Sanjay Chakkoli, Shonali Midha, Vania Phuoc, Jennifer Eatrides, Crystal Erhardt, Ankita K. Patel, Nainesh Parikh, Michael Jaglal
Journal: Blood (2021)
P-POSSUM as mortality predictor in COVID-19-infected patients submitted to emergency digestive surgery. A retrospective cohort study
Authors: Zoilo Madrazo, Javier Osorio, Sebastián Videla, Beatriz Sainz, Araceli Rodríguez-González, Andrea Campos, Maite Santamaría, Amalia Pelegrina, Carmen González-Serrano, Aurora Aldeano, Aingeru Sarriugarte, Carlos Javier Gómez-Díaz, David Ruiz-Luna, Amador García-Ruiz-de-Gordejuela, Concepción Gómez-Gavara, Marta Gil-Barrionuevo, Marina Vila, Arantxa Clavell, Beatriz Campillo, Laura Millán, Carles Olona, Sergi Sánchez-Cordero, Rodrigo Medrano, Camilo Andrés López-Arévalo, Noelia Pérez-Romero, Eva Artigau, Miguel Calle, Víctor Echenagusia, Aurema Otero, Cristian Tebé, Natàlia Pallarès, Sebastiano Biondo
Journal: International Journal of Surgery (2021)
Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplant (ASCT) for Patients with POEMS Syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, Skin Changes): A CIBMTR Analysis
Authors: Ankit Kansagra, Angela Dispenzieri, Raphael Fraser, Noel Estrada-Merly, Shaji Kumar, Muzaffar H. Qazilbash, Nina Shah, Anita D'Souza
Journal: Blood (2021)
A Single-Cell Atlas of Nonhematopoietic Cells in Human Lymph Node and Lymphoma Reveals Landscape of Stromal Remodeling
Authors: Yoshiaki Abe, Mamiko Sakata-Yanagimoto, Manabu Fujisawa, Hiroaki Miyoshi, Yasuhito Suehara, Keiichiro Hattori, Manabu Kusakabe, Tatsuhiro Sakamoto, Hidekazu Nishikii, Tran B. Nguyen, Chikashi Yoshida, Yohei Owada, Tsuyoshi Enomoto, Hiroko Bando, Masahiro Nakayama, Koichi Ohshima, Kensuke Usuki, Tatsuya Oda, Kosei Matsue, Shigeru Chiba
Journal: Blood (2021)
XPO1 Inhibitor (ATG-010) Plus Chemotherapy per Investigator's Choice for Heavily Pretreated Patients with Relapsed or Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL) and Extranodal NK/T-Cell Lymphoma (ENKTL)：Preliminary Results from a Multicenter, Single-Arm, Phase Ib Study (TOUCH Trial)
Authors: Huiqiang Huang, Yan Gao, Huilai Zhang, Keshu Zhou, Jianqiu Wu, Zhen Cai, Hongmei Jing, Lei Fan, Sai Lou, Yizhou Fei, Aihua Wang, Kevin Lynch
Journal: Blood (2021)
Rivaroxaban for Improvement in Thromboembolism Outcomes in Patients with Multiple Myeloma on Lenalidomide-Based Therapy: The Rithmm Feasibility Pilot Trial
Authors: Martha L Louzada, Arleigh McCurdy, Sudeep P Shivakumar, Anthony Quint, Mary Salib, Alejandro Lazo-Langner, Chai Wye Phua, Gregoire Le Gal, Selay Lam, Jenny M. Ho
Journal: Blood (2021)
Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes
Authors: Jusung An, Peter Verwilst, Hira Aziz, Jinwoo Shin, Sungsu Lim, Ilwha Kim, Yun Kyung Kim, Jong Seung Kim
Journal: Bioactive Materials (2021)

The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of β-amyloid (Aβ), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aβ species have been developed, with increasing binding affinities. In the current work, two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ1-42 fibrils —while concurrently preventing poor aqueous solubility—via biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (Kd = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo. These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.
Esophageal Dysmotility Is Associated With Disease Severity in Eosinophilic Esophagitis
Authors: Dustin A. Carlson, Christina Shehata, Nirmala Gonsalves, Ikuo Hirano, Stephanie Peterson, Jacqueline Prescott, Domenico A. Farina, Jacob M. Schauer, Wenjun Kou, Peter J. Kahrilas, John E. Pandolfino
Journal: Clinical Gastroenterology and Hepatology (2021)
STEM-04. PD-1 INDEPENDENT OF PD-L1 LIGATION PROMOTES GLIOBLASTOMA GROWTH THROUGH THE NFkB PATHWAY
Authors: Reza Mirzaei, Wee Yong
Journal: Neuro-Oncology (2021)

Abstract Brain tumor-initiating cells (BTICs) drive glioblastoma growth through not fully understood mechanisms. Here, we found that a proportion of human and murine BTICs expressed programmed cell death protein (PD-1). Gain- or loss-of-function studies revealed that tumor-intrinsic PD-1 promoted proliferation, and self-renewal of BTICs. Mechanistically, site-directed mutagenesis, RNA sequencing and pharmacological inhibitors implicated SHP-2-mediated activation of NFkB downstream of PD-1 in BTICs. Notably, the tumor-intrinsic promoting effects of PD-1 did not require PD-L1 ligation; thus, the therapeutic blocking antibodies inhibiting PD-1/PD-L1 interaction which failed in glioblastoma trials could not overcome the growth advantage of PD-1 in BTICs. Finally, mice with intracranial Pdcd1 over- or underexpressing BTICs had shorter or longer survival, respectively, and this occurred in mice lacking T and B cells. These findings point to a critical role for PD-1 in BTICs and uncover a non-immune resistance mechanism of GBM patients to PD-1 or PD-L1 blocking therapies.