tbuckley/cabot-search huggingface dataset:
ATG and Post-Transplant Cyclophosphamide Predisposes to Inferior Outcome When Using Cryopreserved Stem Cell Grafts
Authors: Igor Novitzky-Basso, Mats Remberger, Carol Chen, Ivan Pasic, Wilson Lam, Arjun Law, Armin Gerbitz, Auro Viswabandya, Jeffrey H. Lipton, Dennis Dong Hwan Kim, Rajat Kumar, Jonas Mattsson, Fotios Michelis
Journal: Blood (2021)
DREAMM-9: Phase I Study of Belantamab Mafodotin Plus Standard of Care in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma
Authors: Saad Z. Usmani, Aránzazu Alonso Alonso, Hang Quach, Youngil Koh, Andreas Guenther, Chang-Ki Min, Xiaoou L. Zhou, Morrys Kaisermann, Lukasz M. Mis, Danaè Williams, Anne Yeakey, Geraldine Ferron-Brady, David J. Figueroa, Brandon E. Kremer, Ira Gupta, Wojciech Janowski
Journal: Blood (2021)
Reprogramming Human Cancer Cells into Antigen Presentation
Authors: Olga Zimmermannova, Ilia Kurochkin, Diego S. Cabrera, Ariane E. Tenreiro, Hreinn Benonisson, Alexandra G. Ferreira, Inês Caiado, David G. Jimenez, Carina Bernardo, Monika Bauden, Yukio Nakamura, Kenichi Miharada, Roland Andersson, Mattias Höglund, Malin Lindstedt, Filipe Pereira
Journal: Blood (2021)
A Phase I Study of the Combination of Venetoclax and Azacitidine in Relapse/Refractory Higher Risk Myelodysplastic Syndrome (MDS)
Authors: Sai Prasad Prasad Desikan, Guillermo Montalban-Bravo, Maro Ohanian, Naval Daver, Musa Yilmaz, Marina Konopleva, Tapan M. Kadia, Sangeetha Venugopal, Heather Schneider, Kelly S. Chien, Rashmi Kanagal-Shamanna, Hagop Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2021)
The Clinical Outcomes and Genomic Landscapes of Acute Lymphoblastic Leukemia Patients with E2A-PBX1: A 10-Year Retrospective Study
Authors: Biqi Zhou, Xinran Chu, Hong Tian, Tianhui Liu, Hong Liu, Wei Gao, Suning Chen, Shaoyan Hu, Depei Wu, Yang Xu
Journal: Blood (2021)
Same sex couple take commissioners to court over “discriminatory” IVF policy
Authors: Abi Rimmer
Journal: BMJ (2021)

A female couple have brought legal proceedings against a clinical commissioning group over its fertility treatment policy.

Megan and Whitney Bacon-Evans have brought judicial review proceedings against NHS Frimley Clinical Commissioning Group in Surrey regarding its in vitro fertilisation policy, which they say discriminates against same sex couples.

Frimley CCG requires same sex couples seeking one cycle of NHS funded IVF treatment to undergo 12 cycles of intrauterine insemination, with six of those being carried out in a clinical setting, costing couples up to around £26 000 (€30 000; $35 000).

In …
Repressed Chromatin Drives Leukaemogenesis in Mutant IDH2 Acute Myeloid Leukaemia Via Inhibition of Granulocyte Differentiation and Cell Cycle Progression
Authors: Douglas RA Silveira, Prodromos Chatzikyriakou, Olena Yavorska, Sarah Mackie, Roan Hulks, Paulina Siejka-Zielinska, Anna Corby, Alastair Smith, Benjamin Brown, Marlen Metzner, Thomas A. Milne, Virginie Penard-Lacronique, Chunxiao Song, Maroof Hasan, Anjan Thakurta, Paresh Vyas, Skirmantas Kriaucionis, Lynn Quek
Journal: Blood (2021)
Abstract 9454: Knowledge, Attitudes, Beliefs of Acute Coronary Syndrome Among Ethiopian Patients Diagnosed With Acute Coronary Syndrome
Authors: Lemlem Demisse, Bekele Alemayehu, Adamu Addissie, Rebecca Gary
Journal: Circulation (2021)

Background: Acute coronary syndrome (ACS) morbidity and mortality is increasing in low to middle-income countries (LMICs) such as Ethiopia. The shift in resources from managing communicable diseases to chronic conditions has brought about formidable health challenges. Purpose: The purpose of this study was to examine the knowledge, attitudes, beliefs among diagnosed ACS patients admitted to one of 3 emergency departments (ED) in Ethiopia. Methods: Sociodemographic (age, gender, education, employment status), clinical (comorbidities) data were collected. Knowledge, attitudes, beliefs about ACS were measured using the modified ACS Response Index questionnaire, with cut-off scores greater than 70% indicating adequate knowledge, attitudes and beliefs about ACS. Data were analyzed using chi-square test and stepwise multivariable logistic regression. Results: Participant’s (N=330) mean age was 57.9 ± 14.1, majority male (n= 219, 66.36%). Over half (N=183, 55.4 %) demonstrated adequate knowledge, attitudes (n=178, 53.9%), and beliefs (n=177, 53.64%) about ACS symptoms. Chest discomfort (n= 274, 83%), fatigue (n=267, 80.9%), chest pain (n=266, 80.6%) were recognized as ACS symptoms. Jaw pain (n=101, 30%) neck pain (n=146 ,44.2%), nausea (n=159,48%), were less recognized. Only (n=104, 31%) of participants indicated they would seek help and only (n=116, 35.1%) would use emergency medical services (EMS). Patients who were &lt;=45 years were 2.16 times more likely to have adequate knowledge than older adults (p=0.014), and females were 2.7 times more knowledgeable than males (p= 0.001). Nondiabetics were 0.52 times less likely to have adequate knowledge compared to diabetics (p= 0.008). Illiteracy was 0.14 times more likely to result in unfavorable attitudes (p&lt;0.001) followed by &lt;= high school education 0.44 (p=0.009). Unemployment was associated with 0.47 odds to have unfavorable attitudes towards ACS (p=0.021). Conclusions: Despite receiving treatment for ACS in an ED, roughly half of the participants had adequate knowledge of symptoms and less than 40% would utilize EMS. Improving EMS and developing educational awareness in Ethiopia are essential for improving symptom identification, appropriate responses and outcomes related to ACS.
Corrigendum to “Near infrared-assisted Fenton reaction for tumor-specific and mitochondrial DNA-targeted photochemotherapy” [Biomaterials 141 (2017) 86–95]
Authors: Ping Hu, Tong Wu, Wenpei Fan, Lei Chen, Yanyan Liu, Dalong Ni, Wenbo Bu, Jianlin Shi
Journal: Biomaterials (2021)
Cost-Effectiveness of Liposomal Cytarabine-Daunorubicin (CPX-351) Compared to Conventional Cytarabine-Daunorubicin Chemotherapy in Acute Myeloid Leukemia
Authors: Jan Philipp Bewersdorf, George Goshua, Kishan K Patel, Rory M. Shallis, Nikolai Podoltsev, Scott F. Huntington, Amer M. Zeidan
Journal: Blood (2021)
Antibody Response after One and/or Two Doses of BNT162b2 Anti- Sars-Cov-2 mRNA Vaccine in Patients Treated By CAR T-Cells Therapy
Authors: Thomas Gastinne, Amandine Le Bourgeois, Marianne Coste-Burel, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Berthe-Marie Imbert, Thomas Drumel, Béatrice Mahé, Viviane Dubruille, Nicolas Blin, Anne Lok, Cyrille Touzeau, Benoit Tessoulin, Maxime Jullien, Sophie Vantyghem, Marie C Bene, Philippe Moreau, Steven Le Gouill, Patrice Chevallier
Journal: Blood (2021)
CAR-T Toxicity Management and Steroid Use in High-Grade B-Cell Lymphoma: Impact on Real-World Survival Outcomes in the UK
Authors: Robin Sanderson, Andrea Kuhnl, Eleni Tholouli, Tobias F Menne, Amit Patel, Sridhar Chaganti, Caroline Besley, Emma Nicholson, Anne-Louise Latif, Ceri Jones, Lourdes Rubio, Charlotte Stenson, Amrith Mathew, Kirsty Sharplin, Jessica Bazin, Lorna Neill, Kathleen Pao Lynn Cheok, Katarzyna Aleksandra Aleksandra Jalowiec, Claire Roddie, Maeve A O'Reilly
Journal: Blood (2021)
Connect ® Lymphoma Disease Registry: A US-Based, Prospective, Observational Cohort Study
Authors: Christopher R. Flowers, David Andorsky, John M. Burke, James R. Cerhan, David L. Grinblatt, Chris L. Pashos, Kathleen Toomey, Andrew D. Zelenetz, Kristen Sullivan, E. Dawn Flick, Pavel Kiselev, Mark Kaplan, Jung Ryun Ahn
Journal: Blood (2021)
Association of Retinal Nerve Fiber Layer Thickness, an Index of Neurodegeneration, With Depressive Symptoms Over Time
Authors: Frank C. T. van der Heide, Indra L. M. Steens, Anouk F. J. Geraets, Yuri D. Foreman, Ronald M. A. Henry, Abraham A. Kroon, Carla J. H. van der Kallen, Thomas T. van Sloten, Pieter C. Dagnelie, Martien C. J. M. van Dongen, Simone J. P. M. Eussen, Tos T. J. M. Berendschot, Jan S. A. G. Schouten, Carroll A. B. Webers, Marleen M. J. van Greevenbroek, Anke Wesselius, Annemarie Koster, Nicolaas C. Schaper, Miranda T. Schram, Seb Köhler, Coen D. A. Stehouwer
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Whether neurodegeneration contributes to the early pathobiology of late-life depression remains incompletely understood. <h3>Objective</h3> To investigate whether lower retinal nerve fiber layer (RNFL) thickness, a marker of neurodegeneration, is associated with the incidence of clinically relevant depressive symptoms and depressive symptoms over time. <h3>Design, Setting, and Participants</h3> This is a population-based cohort study from the Netherlands (The Maastricht Study) with baseline examination between 2010 and 2020 and median (IQR) follow-up of 5.0 (3.0-6.0) years. Participants were recruited from the general population. Individuals with type 2 diabetes were oversampled by design. Data analysis was performed from September 2020 to January 2021. <h3>Exposures</h3> RNFL, an index of neurodegeneration, assessed with optical coherence tomography. <h3>Main Outcomes and Measures</h3> Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)–9 (continuous score, 0-27) at baseline and over time via annual assessments. The presence of clinically relevant depressive symptoms was defined as a PHQ-9 score of 10 or higher. <h3>Results</h3> We used data from 4934 participants with depressive symptoms over time (mean [SD] age, 59.7 [8.4] years; 2159 women [50.8%]; 870 had type 2 diabetes [20.5%]). Lower RNFL thickness was associated with higher incidence of clinically relevant depressive symptoms (per 1 SD, hazard ratio 1.11; 95% CI, 1.01-1.23) and more depressive symptoms over time (per 1 SD, rate ratio, 1.04; 95% CI, 1.01-1.06), after adjustment for demographic, cardiovascular, and lifestyle factors. <h3>Conclusions and Relevance</h3> The findings of this study suggest that lower RNFL thickness is associated with higher incidence of clinically relevant depressive symptoms and more depressive symptoms over time. Hence, neurodegeneration may be associated with the early pathobiology of late-life depression.
The Emergence of the Spike Furin Cleavage Site in SARS-CoV-2
Authors: Yujia Alina Chan, Shing Hei Zhan
Journal: Molecular Biology and Evolution (2021)

Compared with other SARS-related coronaviruses (SARSr-CoVs), SARS-CoV-2 possesses a unique furin cleavage site (FCS) in its spike. This has stimulated discussion pertaining to the origin of SARS-CoV-2 because the FCS has been observed to be under strong selective pressure in humans and confers the enhanced ability to infect some cell types and induce cell-cell fusion. Furthermore, scientists have demonstrated interest in studying novel cleavage sites by introducing them into SARSr-CoVs. We review what is known about the SARS-CoV-2 FCS in the context of its pathogenesis, origin, and how future wildlife coronavirus sampling may alter the interpretation of existing data.
The day a car bomb missed me
Authors: Mary Black
Journal: BMJ (2021)

The day a car bomb missed me Mary Black, It was 1973 and I was a teenager out shopping on the remote off-chance my mother would let me buy a pair of yellow platform boots.They'd be so bad for my feet, she had said, before warning me to take care.Car bombing was on the up in Belfast, but when you normalise risk, you adjust your expectations and the way you live.It was safe enough that day, or so I thought on that busy street.The car exploded as I admired boots in a window display.It blew outward, pieces flying in all directions.A shop window alongside the car shattered in the blast and metal shards pierced the brick wall and flagged pavement.That evening, I lied to my mother about how close I had been.I didn't want to worry her.
Mammalian Ssu72 phosphatase preferentially considers tissue-specific actively transcribed gene expression by regulating RNA Pol II transcription
Authors: Hyun-Soo Kim, Yoon Jeon, Yoon Ok Jang, Ho Lee, Yong Shin, Chang-Woo Lee
Journal: Theranostics (2021)

Reversible phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) is essential for gene expression control. How altering the phosphorylation of the CTD contributes to gene expression in mammalian systems remains poorly understood. Methods: Primary mouse embryonic fibroblasts, hepatocytes, and embryonic stem cells were isolated from conditional Ssu72f/f mice. To knockout the mouse Ssu72 gene, we infected the cells with adenoviruses of incorporated luciferase and Cre recombinase, respectively. RNA sequencing, ChIP sequencing, ChIP assay, immunoblot analyses, qRT-PCR assay, and immunostaining were performed to gain insights into the functional mechanisms of Ssu72 loss in Pol II dynamics. Results: Using primary cells isolated from Ssu72 conditional knockout and transgenic mice, we found that mammalian Ssu72-mediated transcriptional elongation rather than polyadenylation or RNA processing contributed to the transcriptional regulation of various genes. Depletion of Ssu72 resulted in aberrant Pol II pausing and elongation defects. Reduced transcriptional elongation efficiency tended to preferentially affect expression levels of actively transcribed genes in a tissue-specific manner. Furthermore, Ssu72 CTD phosphatase seemed to regulate the phosphorylation levels of CTD Ser2 and Thr4 through accurate modulation of P-TEFb activity and recruitment. Conclusions: Our findings demonstrate that mammalian Ssu72 contributes to the transcription of tissue-specific actively transcribed gene expression by regulating reciprocal phosphorylation of Pol II CTD.
Donor Genetic Determinant of Thymopoiesis rs2204985 Impacts Clinical Outcome after Single HLA Mismatched HSCT
Authors: Chrysanthi Tsamadou, Sowmya Gowdavally, Uwe Platzbecker, Elisa Sala, Thomas Valerius, Gerald Wulf, Eva Maria Wagner, Nicolaus Kroeger, Niels Murawski, Hermann Einsele, Kerstin Schaefer-Eckart, Sebastian Freitag, Jochen Casper, Martin Kaufmann, Mareike Dürholt, Bernd Hertenstein, Stefan Klein, Mark Ringhoffer, Christine Neuchel, Immanuel Rode, Joannis Mytilineos, Hubert Schrezenmeier, Daniel Fürst
Journal: Blood (2021)
OCEAN (OP-103): Melflufen/Dexamethasone (Dex) Compared with Pomalidomide (Pom)/Dex in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) - Safety and Tolerability Analyses
Authors: Paul G. Richardson, Fredrik H. Schjesvold, Haifaa Abdulhaq, Daniel Coriu, Antonio Lazzaro, Pieter Sonneveld, Torbjörn Kullenburg, Johan Harmenberg, Marcus Thuresson, Catriona Byrne, María-Victoria Mateos
Journal: Blood (2021)
Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission after 5-Azacitidine and Venetoclax: A Multicenter Retrospective Study
Authors: Oren Pasvolsky, Shai Shimony, Ron Ram, Avichai Shimoni, Liat Shargian-Alon, Batia Avni, Ofir Wolach, Tzippy Shochat, Ronit Yerushalmi, Odelia Amit, Pia Raanani, Moshe Yeshurun
Journal: Blood (2021)
m6A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer
Authors: Zhihui Zhang, Chaoqi Zhang, Zhaoyang Yang, Guochao Zhang, Peng Wu, Yuejun Luo, Qingpeng Zeng, Lide Wang, Qi Xue, Yi Zhang, Nan Sun, Jie He
Journal: Journal of Hematology & Oncology (2021)

Abstract Small-cell lung cancer (SCLC) is a devastating subtype of lung cancer with few therapeutic options. Despite the advent of immunotherapy, platinum-based chemotherapy is still the irreplaceable first-line therapy for SCLCs. However, drug resistance will invariably occur in most patients and the outcomes are heterogeneous. Therefore, clinically feasible classification strategies and potential therapeutic targets for overcoming chemotherapy resistance are urgently needed. N 6 -methyladenosine (m 6 A) is a novel epigenetic decisive factor that is involved in tumor progression and drug resistance. However, almost nothing is known about m 6 A modification in SCLC. Here, we assessed 200 SCLC samples from patients who underwent chemotherapy from three different cohorts, including a validation cohort containing 71 cases with qPCR data and an independent cohort containing 79 cases with immunohistochemistry data (quantified as H-score). We systematically characterized the predictive landscape of m 6 A regulators in SCLC patients following with chemotherapy. Using the LASSO Cox model, we built a seven-regulator-based ( ZCCHC4 , IGF2BP3 , ALKBH5 , YTHDF3 , METTL5 , G3BP1 , and RBMX ) chemotherapy benefit predictive classifier (m 6 A score) and subsequently validated the classifier in two other cohorts. Time-dependent ROC and C-index analyses showed that the m 6 A score to possessed superior predictive power for chemotherapy benefit in comparison with other clinicopathological parameters. A multicohort multivariate analysis revealed that the m 6 A score is an independent factor that affects survival benefit across multiple cohorts. Our in vitro experimental results revealed that three regulators—ZCCHC4, G3BP1, and RBMX—may serve as promising novel therapeutic targets for overcoming chemoresistance in SCLCs. Our results, for the first time, demonstrate the predictive significance of m 6 A regulators for chemotherapy benefit, as well as their potential as therapeutic targets for overcoming chemotherapy resistance in SCLC patients. The m 6 A score was found to be a reliable prognostic tool that may help guide chemotherapy decisions for patients with SCLC.
Abstract 14581: Impact of Heart Failure on 30-day Readmissions After Transcatheter Left Atrial Appendage Occlusion With the Watchman Device
Authors: Abdelrhman Abumoawad, Islam Shatla, Waseem Wahood, Ahmed Nagy, Azizullah Beran, Mohammed Mhanna, Kirolos Barssoum, Hamza A Rayes, Poghni A Peri-okonny, Anthony Magalski, Omair Yousuf, Angel Lopez-candales
Journal: Circulation (2021)

Background: The Watchman device reduces the risk of stroke in select patients with atrial fibrillation (AF). AF commonly coexists with heart failure (HF) and these conditions harbor interrelated pathophysiological mechanisms and treatment strategies., the impact of comorbid heart failure on outcomes in patients with AF undergoing Watchman device implantation remains unclear. Methods: We identified patients from the Nationwide Readmission Database who underwent Watchman device placement between 2014-2018 using ICD-9 and 10 codes. Patients were classified into 2 groups based on the presence of HF. Outcomes were all-cause and cause-specific 30-day readmissions and mortality rate during readmission. Kaplan-Meier analysis was used to assess the association of HF with 30-day hospital readmission. Results: We identified 18,349 recipients, 13,180 had no heart failure (NHF) while 5169 had HF. Mean age was similar between both groups. A total of 789 (5.9%) were readmitted within 30 days in the NHF compared to 439 (8.5%) in the non HF (NHF) group, The 30-day readmission rate was higher and Length of the stay was slightly longer in HF group. Prior stroke was more prevalent in the NHF group. Coronary artery disease, smoking, prior ICD, and obesity were more prevalent among HF group as demonstrated in table 1. The most common causes of readmissions for NHF vs HF were (acute heart failure: 15 vs 30%, p&lt;0.001), (GI bleed: 19 vs 23%, P=0.16), and (AKI: 19 vs 27%, P&lt;0.002). No difference in mortality or time-to readmission observed between both groups (Fig.1). Conclusion: In this analysis, post-Watchman 30-day readmission frequency was higher in patients with HF compared with NHF, though the time-to readmission was similar. Interestingly, 1 in 7 patients with NHF at baseline was readmitted with acute HF. Additional studies are now needed to identify which triggers are responsible for these readmissions so that effective preventive efforts can be instituted to reduce these readmissions.
Allosteric Inhibition of MALT1 Is Efficacious in a Model of Chronic Graft-Versus-Host Disease and Modulates Immunometabolic Activation
Authors: Joanna R Dispirito, Mehmet G Badur, Subhabrata 'Brad' Biswas, Diogo M Camacho, Aditi Chalishazar, Brian DeChristopher, Katie Sellers, Mya Steadman, Keng Soh, John Monroe, Andrew Long
Journal: Blood (2021)
Association of Nephrin Gene Polymorphisms With Type 2 Diabetes in a Japanese Population
Authors: Makoto Daimon, Guijin Ji, Toshihide Oizumi, Takashi Kido, Masanori Baba, Yumi Jimbu, Wataru Kameda, Shinji Susa, Hiroshi Yamaguchi, Hiroshi Ohnuma, Masaaki Muramatsu, Takeo Kato
Journal: Diabetes Care (2006)

Nephrin is a major component of the glomerular filtration barrier, and its expression was at first thought to be specific to kidney glomerular podocytes (1). However, it was later found in nonrenal tissues, such as the pancreas (2–4), as well. Several studies (2,3,5) have shown the expression of nephrin in human pancreatic islet cells. Therefore, nephrin may play some roles in the pancreatic islet and, thus, may be involved in the pathophysiology leading to diabetes. We here examined the association of the nephrin gene polymorphisms with type 2 diabetes.

The associations of three single nucleotide polymorphisms (SNPs) (C294T, −61C/G, and C2289T) of the nephrin gene with diabetes were examined using two (first and second) sample sets (diabetes, n = 72 and 31, respectively; impaired glucose tolerance [IGT], n = 75 and 77, respectively; and normal glucose tolerance [NGT], n = 227 and 244, respectively) from the cohort population of the Funagata Study, a Japanese community-based study (6). The study conditions were the same as those in our previous report (7).

Three SNPs in the nephrin gene (C to T at nucleotide position 294 in exon 3 from the translation intitiation codon ATG (C294T) (JSNP database ID: IMS-JST 035656), C to G in intron 5 at nucleotide position 61 upstream from the intron 5/exon 6 splicing site …