tbuckley/cabot-search huggingface dataset:
Changes in Prostate-Specific Antigen Testing Relative to the Revised US Preventive Services Task Force Recommendation on Prostate Cancer Screening
Authors: Michael S. Leapman, Rong Wang, Henry Park, James B. Yu, Preston C. Sprenkle, Matthew R. Cooperberg, Cary P. Gross, Xiaomei Ma
Journal: JAMA Oncology (2021)

In April 2017, the US Preventive Services Task Force (USPSTF) published a draft guideline that reversed its 2012 guidance advising against prostate-specific antigen (PSA)-based screening for prostate cancer in all men (grade D), instead endorsing individual decision-making for men aged 55 to 69 years (grade C).To evaluate changes in rates of PSA testing after revisions in the USPSTF guideline on prostate cancer screening.This retrospective cohort study used deidentified claims data from Blue Cross Blue Shield beneficiaries aged 40 to 89 years from January 1, 2013, through December 31, 2019.Publication of the USPSTF's draft (April 2017) and final (May 2018) recommendation on prostate cancer screening.Age-adjusted rates of PSA testing in bimonthly periods were calculated, and PSA testing rates from calendar years before (January 1 to December 31, 2016) and after (January 1 to December 31, 2019) the guideline change were compared. Interrupted time series analyses were used to evaluate the association of the draft (April 2017) and published (May 2018) USPSTF guideline with rates of PSA testing. Changes in rates of PSA testing were further evaluated among beneficiaries within the age categories reflected in the guideline: 40 to 54 years, 55 to 69 years, and 70 to 89 years.The median number of eligible beneficiaries for each bimonthly period was 8 087 565 (range, 6 407 602-8 747 308), and the median age of all included eligible beneficiaries was 53 years (IQR, 47-59 years). Between 2016 and 2019, the mean (SD) rate of PSA testing increased from 32.5 (1.1) to 36.5 (1.1) tests per 100 person-years, a relative increase of 12.5% (95% CI, 1.1%-24.4%). During the same period, mean (SD) rates of PSA testing increased from 20.6 (0.8) to 22.7 (0.9) tests per 100 person-years among men aged 40 to 54 years (relative increase, 10.1%; 95% CI, -2.8% to 23.7%), from 49.8 (1.9) to 55.8 (1.8) tests per 100 person-years among men aged 55 to 69 years (relative increase, 12.1%; 95% CI, -0.2% to 25.2%), and from 38.0 (1.4) to 44.2 (1.4) tests per 100 person-years among men aged 70 to 89 years (relative increase, 16.2%; 95% CI, 4.2%-29.0%). Interrupted time series analysis revealed a significantly increasing trend of PSA testing after April 2017 among all beneficiaries (0.30 tests per 100 person-years for each bimonthly period; P < .001).This large national cohort study found that rates of PSA testing increased after the USPSTF's draft statement in 2017, reversing trends seen after earlier guidance against PSA testing for all patients. Increased testing was also observed among older men, who may be less likely to benefit from prostate cancer screening.
<i>In Vivo</i> CRISPR-Cas9 Screens in PDX Models Reveals ADAM10 As Novel Therapeutic Target in Acute Leukemia
Authors: Ehsan Bahrami, Jan Philipp Schmid, Martin Becker, Anna-Katharina Wirth, Rupert Öllinger, Roland Rad, Binje Vick, Ashok Kumar Jayavelu, Matthias Mann, Tobias Herold, Irmela Jeremias
Journal: Blood (2021)
The Immediate Effect of COVID-19 Vaccination on Anticoagulation Control in Patients Using Vitamin K Antagonists
Authors: Chantal Visser, Joseph S. Biedermann, Melchior C. Nierman, Felix J. M. Van der Meer, Anouk J. W. Gulpen, Yvonne C. F. Moors, Suzanne C. Cannegieter, Willem M Lijfering, Marieke J.H.A. Kruip, The Dutch COVID & Thrombosis Coalition
Journal: Blood (2021)
Silent Cerebral Infarction on Brain MRI Is Associated with Cognitive Impairment in Ittp Survivors in Hematological Remission
Authors: Jia Yu, Aria Wei, Xiang-Zuo Pan, Gloria Frances Gerber, Sarah Hussain, Alison R. Moliterno, Michael B. Streiff, Peggy Kraus, Claire Logue, Jennifer Yui, Rakhi P. Naik, Hira Latif, Ruhail Kohli, Sophie M. Lanzkron, Evan M. Braunstein, Robert Brodsky, Doris Lin, Shruti Chaturvedi
Journal: Blood (2021)
Galectin-3 Signaling in Donor T Cells Regulates Acute Graft Versus Host Disease (aGvHD) after Allogenic Transplantation
Authors: Hemn Mohammadpour, Takemasa Tsuji, Cameron R. MacDonald, Joseph L. Sarow, Jingxin Qiu, Junko Matsuzaki, Kristopher Attwood, Bruce R. Blazar, Kunle Odunsi, Elizabeth A. Repasky, Philip L. McCarthy
Journal: Blood (2021)
Venetoclax, Obinutuzumab and Atezolizumab (PD-L1 Checkpoint Inhibitor) for First-Line Treatment for Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Nitin Jain, Alessandra Ferrajoli, Musa Yilmaz, Philip A. Thompson, Marina Konopleva, Michael R Green, Deepa Sampath, Sattva S. Neelapu, Koichi Takahashi, Lucia Masarova, Jan A. Burger, Rashmi Kanagal-Shamanna, Joseph D. Khoury, Naveen Garg, Xiaoping Su, Xuemei Wang, Hinalben Patel, Ana Ayala, Hagop Kantarjian, Michael J. Keating, William G. Wierda
Journal: Blood (2021)
Single-Arm Phase 1b/2 Trial of the PI3Kδ Inhibitor Linperlisib Combining with Gemox in Relapsed and/or Refractory Diffuse Large B Cell Lymphoma
Authors: Zhiming Li, Haiyan Yang, Hong Cen, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu
Journal: Blood (2021)
T-cell intrinsic Toll-like receptor signaling: implications for cancer immunotherapy and CAR T-cells
Authors: Yasmin Nouri, Robert Weinkove, Rachel Perret
Journal: Journal for ImmunoTherapy of Cancer (2021)

Toll-like receptors (TLRs) are evolutionarily conserved molecules that specifically recognize common microbial patterns, and have a critical role in innate and adaptive immunity. Although TLRs are highly expressed by innate immune cells, particularly antigen-presenting cells, the very first report of a human TLR also described its expression and function within T-cells. Gene knock-out models and adoptive cell transfer studies have since confirmed that TLRs function as important costimulatory and regulatory molecules within T-cells themselves. By acting directly on T-cells, TLR agonists can enhance cytokine production by activated T-cells, increase T-cell sensitivity to T-cell receptor stimulation, promote long-lived T-cell memory, and reduce the suppressive activity of regulatory T-cells. Direct stimulation of T-cell intrinsic TLRs may be a relevant mechanism of action of TLR ligands currently under clinical investigation as cancer immunotherapies. Finally, chimeric antigen receptor (CAR) T-cells afford a new opportunity to specifically exploit T-cell intrinsic TLR function. This can be achieved by expressing TLR signaling domains, or domains from their signaling partner myeloid differentiation primary response 88 (MyD88), within or alongside the CAR. This review summarizes the expression and function of TLRs within T-cells, and explores the relevance of T-cell intrinsic TLR expression to the benefits and risks of TLR-stimulating cancer immunotherapies, including CAR T-cells.
Abstract 9390: Mechanical Circulatory Support and Outcomes in Women versus Men
Authors: Nicole Pristera, Zachary Il'Giovine, Weili Zheng, Beka Bakhtadze, Leslie Cho
Journal: Circulation (2021)

Introduction: There has been a substantial increase in the use of temporary mechanical circulatory support (MCS) in cardiac intensive care, particularly driven by Impella and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Sex-specific data in patients with MCS are limited. We report our single-center experience on characteristics and outcomes of women versus men supported with MCS. Methods: This was a retrospective study of all patients receiving Impella CP, 5.0, or 5.5 and/or VA-ECMO in our cardiac intensive care unit from January 1, 2019 to December 31, 2020. Primary outcomes were death and major MCS-associated complications, including bleeding, neurologic, and limb events as defined by the Extracorporeal Life Support Organization. Results: 167 adult patients were included (22% female). Baseline characteristics between women and men were significantly different (Table). Non-acute myocardial infarction cardiogenic shock was the leading indication for MCS in both sexes. Impella CP was used most frequently in women, with only 3 (8.1%) women receiving Impella 5.0/5.5. In contrast, 50 (38.5%) men had Impella 5.0/5.5. VA-ECMO use was also lower in women (14.6% versus 33.1%, p=0.04). There was a trend toward higher bleeding, neurologic, and limb events in women, not statistically significant (35.1% vs 30.8%, p=0.61; 8.1% vs 2.3%, p=0.09; 21.6% vs 12.3%, p=0.15). In-hospital mortality was similar between women and men (43.2% vs 41.5%, p=0.85). Among survivors, women and men were equally likely to be discharged home (47.6% vs 57.9%, p=0.4). Conclusions: There were notable differences in baseline characteristics and device selection among women and men requiring MCS. There was a trend toward higher major complication rates in women, not reaching statistical significance likely due to small sample size with low number of events. Larger studies are needed to further explore sex-specific risk factor profiles and outcomes in the MCS population.
Abstract 10007: AMP Deaminase in Mitochondria-Associated ER Membranes Contributes to Reduction of the Threshold for Mitochondrial Permeability Transition in Type 2 Diabetic Hearts
Authors: Arata Osanami, Masaya Tanno, Atsushi Kuno, Hidemichi Kouzu, Toshiyuki Yano, Tatsuya Sato, Tetsuji Miura, Toshifumi Ogawa
Journal: Circulation (2021)

Introduction: Despite the growing clinical burden of diabetic cardiomyopathy, there is no specific treatment for the disorder. We previously demonstrated that increased activity of AMP deaminase (AMPD) contributes to diastolic dysfunction in diabetic myocardium through ATP depletion and augmentation of xanthine oxidase-mediated ROS production. Additionally, the threshold for mitochondrial permeability transition (mPT), a major mechanism of cell necrosis, was found to be reduced by diabetes. Hypothesis: Increased localization of AMPD in mitochondria-associated ER membranes (MAMs) lowers the threshold for mPT, via accelerated Ca 2+ transport from the ER, by interaction with IP3 receptor (IP3R), VDAC and/or mitochondrial Ca 2+ uniporter (MCU). Methods and Results: The 90-kDa full-length and 70-kDa N-terminus-truncated form of AMPD3, a main isoform in rat hearts, were detected in the myocardium. The 90-kDa full-length AMPD3 was exclusively observed in outer mitochondrial membranes (OMMs), and both 90-kDa AMPD3 and 70-kDa AMPD3 were observed in MAMs. The 90-kDa AMPD3 levels in OMMs and MAMs were significantly higher in OLETF, type 2 diabetic rats, than in LETO, non-diabetic control rats, while 70-kDa AMPD3 levels were comparable in OLETF and LETO. The area of the MAM quantified by using electron micrographs was 57% larger in OLETF than in LETO (p&lt;0.05). Immunoprecipitation experiments showed that 90-kDa AMPD3 was associated with VDAC, whereas 70-kDa AMPD3 did not interact with IP3R, VDAC or MCU. Ca 2+ retention capacity (CRC), an index of the threshold for mPT, analyzed in MAM-containing crude mitochondria was 21% lower in OLETF than in LETO (p&lt;0.05). Although an inhibitor of AMPD (cpd3) had no effect on CRC, knockdown of 90-kDa AMPD3 significantly ameliorated H 2 O 2 -induced loss of mitochondrial membrane potential that was determined by TMRE in cultured isolated cardiomyocytes. Conclusions: The results suggest that 90-kDa AMPD3 in MAMs plays a role in regulation of the mPT threshold in a deaminase activity-independent manner and that increased AMPD3 in MAMs contributes to mitochondrial respiratory dysfunction in diabetic myocardium.
Abstract 12656: Atrial Speckle Tracking Echocardiography for Detecting Atrial Fibrillation in Cryptogenic Stroke: A Meta-Analysis
Authors: Mohab Hassib, Kiro Barssoum, Medhat Chowdhury, Sarath Lal Mannumbeth Renjithlal, Abdelrhman Abumoawad, Steven Hamilton, Ahmed Elkhouly, Muhammad Haq, George Bchech, Vivek Bhat, Varun Victor, Ashish Kumar
Journal: Circulation (2021)

Introduction: Cryptogenic stroke (CS) accounts for approximately twenty-five percent of ischemic stroke cases with atrial fibrillation (AF) accounting for thirty percent of CS cases. We aimed to investigate the utility of atrial speckle tracking (STE) in identifying patients at high risk of AF after CS and potentially guiding patients who will benefit from long term rhythm monitoring devices. Methods: Cochrane Library, MEDLINE, and EMBASE were searched for relevant studies. We included studies that examined patients with new CS without a history of AF, and further examined LA strain parameters (peak and/or reservoir strain). Continuous data were pooled as a mean difference (MD) comparing patients who developed AF versus(vs) no AF. We used inverse variance method with Paule-Mandel estimator for tau2 and Hartung-Knapp adjustment, for random effect analysis. Hazard ratios were pooled using a similar statistical method. I2 was used to assess heterogeneity. Results: Eleven observational studies met our criteria, and included 2834 patients with new CS. Of those, 377 patients developed AF on follow up and 2457 patients did not develop AF. The AF group vs no AF had significantly reduced LA reservoir strain (LARS) [MD: -8.95; 95% CI: -11.33, -6.57) I2= 85%, p&lt;0.001] at presentation. Further, a higher LARS was associated with a significantly lower incidence of AF after CS[HR: 0.93; 95%CI:0.89, 0.97)I2=0%]. Conclusion: Atrial reservoir strain is significantly lower in patients who developed AF after CS and a lower value is predictive of AF. More studies are needed to validate this data.
The EQ-5D-5L Predicts Treatment Outcomes and Provides Added Value to the R-IPSS in Patients with MDS, CMML or AML Treated within the Austrian Azacitidine Registry - a Prospective Cohort Study By the AGMT Study Group
Authors: Lisa Pleyer, Sonja Heibl, Christoph Tinchon, Sonja Vallet, Branka Petricevic, Michael Leisch, Alexander Egle, Thomas Melchardt, Gudrun Piringer, Dominik Wolf, Richard Beswick, Manuel Drost, Julian Larcher-Senn, Thomas Grochtdreis, Richard Greil, Reinhard Stauder
Journal: Blood (2021)
Endoscopic treatment of rectovesical fistula after colorectal anastomosis: tube-in-tube endoscopic vacuum therapy method
Authors: Marcelo Simas de Lima, Caio Almeida Perez, John Alexander Lata Guacho, Marcelo Mochate Flor, Marina Tucci, Marina Ferreira, Fauze Maluf-Filho
Journal: Endoscopy (2021)

A 56-year-old man underwent rectosigmoidectomy, partial cystectomy, and derivative colostomy for locally advanced distal rectal adenocarcinoma, persistent after chemoradiation. On the 25th postoperative day, he presented clinical worsening and increased abdominal drain output, and was submitted to tomography with intravesical contrast infusion, which showed a rectovesical fistula communicating with the surgical drain ([Fig. 1]).
NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis
Authors: Vangelis Kondylis, Apostolos Polykratis, Hanno Ehlken, Laura Ochoa-Callejero, Beate Katharina Straub, Santosh Krishna-Subramanian, Trieu-My Van, Harald-Morten Curth, Nicole Heise, Falk Weih, Ulf Klein, Peter Schirmacher, Michelle Kelliher, Manolis Pasparakis
Journal: Cancer Cell (2015)

(Cancer Cell 25, 582–598; November 9, 2015) The abbreviated term NF-κB was incorrectly defined as “necrosis factor κB” instead of the correct definition, “nuclear factor κB,” on three occasions in the manuscript: in the Summary (pp. 582), Significance (pp. 582), and Introduction (pp. 584) sections. This has now been corrected in the article online. We apologize for the error and any confusion it may have caused. NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte ApoptosisKondylis et al.Cancer CellNovember 09, 2015In BriefKondylis et al. identify an NF-κB-independent function of NEMO in controlling RIPK1 kinase activity-dependent apoptosis of hepatocytes and thus hepatocarcinogenesis. NEMO-mediated NF-κB activity and kinase activity-independent scaffold function of RIPK1 also regulate hepatocyte apoptosis. Full-Text PDF Open Access
Abstract 9322: Internal Medicine Resident Education Improves Cardiac Rehabilitation Knowledge, Attitudes, and Referral Rates
Authors: Nare Torosyan, Maggie Wang, C Bairey Merz, Janet Wei, Chrisandra Shufelt
Journal: Circulation (2021)

Introduction: Cardiac rehabilitation (CR) remains underutilized despite known benefits. Residency training may be an opportunity to address barriers to CR referrals, including physician knowledge gaps and unfamiliarity with referral processes. We sought to investigate the impact of resident education on knowledge and attitudes towards CR in a pilot study. Methods: Voluntary CR survey was sent to 20 internal medicine residents in a primary care clinic using an online-based platform. Following survey completion, residents received a scripted educational lecture and handout on CR. Surveys were redistributed 2 months post-education. Mean aggregate knowledge scores and attitude ratings on a 5-point Likert scale pre- and post-education were analyzed using paired t-tests. Referral rates of eligible patients 2 months pre- and post- education were analyzed using Fisher’s exact test. Results: Sixteen (80%) residents responded to both pre- and post-education surveys. Thirteen residents (81%) reported no education on CR within the past year. There was a significant increase in aggregate knowledge scores on CR components (5.1 ± 2.1 vs 7.0 ± 1.4, p = 0.001), insurance coverage (2.4 ± 1.8 vs 5.6 ± 0.7, p &lt; 0.0001), and eligible diagnoses (7.1 ± 4.8 vs 9.9 ± 3.4, p = 0.03) following education (figure). Resident attitude ratings also improved after education, particularly in comfort level explaining CR (3.69 ± 1.30 vs. 2.06 ± 1.06, p &lt; 0.0001) and familiarity with the referral process (4.00 ± 1.15 vs. 2.18 ± 1.11, p &lt; 0.0001). CR referrals increased from 0% (0 out of 10 eligible patients) to 33% (3 out of 9 eligible patients) post-education ( p = 0.09). Conclusions: Internal medicine resident knowledge and attitudes towards CR significantly improved after education and may play an important role in facilitating CR referrals. Future studies on optimizing strategies for incorporation of CR education into the residency curriculum is needed.
Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies
Authors: Sven Kratochvil, Chen-Hsiang Shen, Ying-Cing Lin, Kai Xu, Usha Nair, Lais Da Silva Pereira, Prabhanshu Tripathi, Johan Arnold, Gwo-Yu Chuang, Eleonora Melzi, Arne Schön, Baoshan Zhang, Marlon Dillon, Brian Bonilla, Barbara J. Flynn, Kathrin H. Kirsch, Neville K. Kisalu, Patience K. Kiyuka, Tracy Liu, Li Ou, Marie Pancera, Reda Rawi, Mateo Reveiz, Kareen Seignon, Lawrence T. Wang, Michael T. Waring, John Warner, Yongping Yang, Joseph R. Francica, Azza H. Idris, Robert A. Seder, Peter D. Kwong, Facundo D. Batista
Journal: Immunity (2021)

Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors and used both vaccination and bioinformatic analysis to obtain variant CIS43 antibodies with improved protective capacity. One such antibody, iGL-CIS43.D3, was significantly more potent than the current best-in-class PfCSP-directed antibody. We found that vaccination with a junctional epitope peptide was more effective than full-length PfCSP at recruiting iGL-CIS43 B cells to germinal centers. Structure-function analysis revealed multiple somatic hypermutations that combinatorically improved protection. This mouse model can thus be used to understand vaccine immunogens and to develop highly potent anti-malarial antibodies.
Automated Disease Classification Using Whole Genome Sequencing (WGS) and Whole Transcriptome Sequencing (WTS) Data with Transparent Artificial Intelligence (AI)
Authors: Niroshan Nadarajah, Erika Pelaez Coyotl, James Golden, Stephan Hutter, Tamas Madl, Manja Meggendorfer, Wencke Walter, Liwen You, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach
Journal: Blood (2021)
Characterization of Informed Consent Forms Posted on ClinicalTrials.gov
Authors: Tony Tse, Sarah White, Luke Gelinas, Walker Morrell, Barbara Bierer, Deborah A. Zarin
Journal: JAMA Network Open (2021)

This cross-sectional study examines available forms and posting trends of registered trials as well as the frequency of form posting by funder type for trials initiated since the revised Common Rule was implemented.
Unique Characteristics and Outcomes of Therapy-Related Acute Lymphoblastic Leukemia (trALL) Following Therapy for Multiple Myeloma (MM)
Authors: Ricardo D Parrondo, Zaid Abdel Rahman, Michael G. Heckman, Mikolaj Wieczorek, Liuyan Jiang, Hassan B. Alkhateeb, Mark R. Litzow, Patricia Greipp, Taimur Sher, Leif Bergsagel, Rafael Fonseca, Vivek Roy, Angela Dispenzieri, Mohamed A. Kharfan-Dabaja, Hemant S. Murthy, Sikander Ailawadhi, James M. Foran
Journal: Blood (2021)
Re: Can Negative Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Avoid the Need for Pelvic Lymph Node Dissection in Newly Diagnosed Prostate Cancer Patients? A Systematic Review and Meta-analysis with Backup Histology as Reference Standard
Authors: Vito Pansadoro, Aldo Brassetti
Journal: European Urology (2021)
Self-Efficacy for Symptom Management in Long-Term Adult Hematopoietic Stem Cell Survivors
Authors: Nosha Farhadfar, Michael Weaver, Zeina Al-Mansour, Jean C. Yi, Heather S. L. Jim, Alison W. Loren, Navneet S. Majhail, Victoria Whalen, John R. Wingard, Debra Lynch Kelly, Karen Syrjala
Journal: Blood (2021)
Deletion of CISH and TGFβR2 in iPSC-Derived NK Cells Promotes High Cytotoxicity and Enhances <i>In Vivo</i> Tumor Killing
Authors: Alexandra Gerew, Steven Sexton, Kevin M Wasko, Mark S Shearman, Kate Zhang, Kai-Hsin Chang, Samia Q. Khan
Journal: Blood (2021)
Accurate long-read de novo assembly evaluation with Inspector
Authors: Yu Chen, Yixin Zhang, Amy Y. Wang, Min Gao, Zechen Chong
Journal: Genome biology (2021)

Long-read de novo genome assembly continues to advance rapidly. However, there is a lack of effective tools to accurately evaluate the assembly results, especially for structural errors. We present Inspector, a reference-free long-read de novo assembly evaluator which faithfully reports types of errors and their precise locations. Notably, Inspector can correct the assembly errors based on consensus sequences derived from raw reads covering erroneous regions. Based on in silico and long-read assembly results from multiple long-read data and assemblers, we demonstrate that in addition to providing generic metrics, Inspector can accurately identify both large-scale and small-scale assembly errors.