tbuckley/cabot-search huggingface dataset:
Single-Incision Mini-Slings for Stress Urinary Incontinence in Women
Authors: Mohamed Abdel-Fattah, David Cooper, Tracey Davidson, Mary Kilonzo, Md Hossain, Dwayne Boyers, Kiron Bhal, Judith Wardle, James N'Dow, Graeme MacLennan, John Norrie
Journal: New England Journal of Medicine (2022)

Until recently, synthetic midurethral slings (made of mesh or tape) were the standard surgical treatment worldwide for female stress urinary incontinence, if conservative management failed. Data comparing the effectiveness and safety of newer single-incision mini-slings with those of standard midurethral slings are limited.We performed a pragmatic, noninferiority, randomized trial comparing mini-slings with midurethral slings among women at 21 U.K. hospitals during 36 months of follow-up. The primary outcome was patient-reported success (defined as a response of very much or much improved on the Patient Global Impression of Improvement questionnaire) at 15 months after randomization (approximately 1 year after surgery). The noninferiority margin was 10 percentage points.A total of 298 women were assigned to receive mini-slings and 298 were assigned to receive midurethral slings. At 15 months, success was reported by 212 of 268 patients (79.1%) in the mini-sling group and by 189 of 250 patients (75.6%) in the midurethral-sling group (adjusted risk difference, 4.6 percentage points; 95% confidence interval [CI], -2.7 to 11.8; P<0.001 for noninferiority). At the 36-month follow-up, success was reported by 177 of 246 patients (72.0%) and by 157 of 235 patients (66.8%) in the respective groups (adjusted risk difference, 5.7 percentage points; 95% CI, -1.3 to 12.8). At 36 months, the percentage of patients with groin or thigh pain was 14.1% with mini-slings and 14.9% with midurethral slings. Over the 36-month follow-up period, the percentage of patients with tape or mesh exposure was 3.3% with mini-slings and 1.9% with midurethral slings, and the percentage who underwent further surgery for stress urinary incontinence was 2.5% and 1.1%, respectively. Outcomes with respect to quality of life and sexual function were similar in the two groups, with the exception of dyspareunia; among 290 women responding to a validated questionnaire, dyspareunia was reported by 11.7% in the mini-sling group and 4.8% in the midurethral-sling group.Single-incision mini-slings were noninferior to standard midurethral slings with respect to patient-reported success at 15 months, and the percentage of patients reporting success remained similar in the two groups at the 36-month follow-up. (Funded by the National Institute for Health Research.).
Integrated Analysis of Ovarian Juvenile Granulosa Cell Tumors Reveals Distinct Epigenetic Signatures and Recurrent <i>TERT</i> Rearrangements
Authors: Theodore Vougiouklakis, Kelsey Zhu, Varshini Vasudevaraja, Jonathan Serrano, Guomiao Shen, Rebecca L. Linn, Xiaojun Feng, Sarah Chiang, Julieta E. Barroeta, Kristen M. Thomas, Lauren E. Schwartz, Pratibha S. Shukla, Anais Malpica, Esther Oliva, Paolo Cotzia, Deborah F. DeLair, Matija Snuderl, George Jour
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Adult granulosa cell tumor (AGCT) is characterized by the somatic FOXL2 p.C134W mutation, and recurrences have been associated with TERT promoter and KMT2D-truncating mutations. Conversely, the molecular underpinnings of the rare juvenile granulosa cell tumor (JGCT) have not been well elucidated. To this end, we applied a tumor-only integrated approach to investigate the genomic, transcriptomic, and epigenomic landscape of 31 JGCTs to identify putative oncogenic drivers. Experimental Design: Multipronged analyses of 31 JGCTs were performed utilizing a clinically validated next-generation sequencing (NGS) panel targeting 580 cancer-related genes for genomic interrogation, in addition to targeted RNA NGS for transcriptomic exploration. Genome-wide DNA methylation profiling was conducted using an Infinium Methylation EPIC array targeting 866,562 CpG methylation sites. Results: We identified frequent KMT2C-truncating mutations along with other mutated genes implicated in the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, in addition to previously reported hotspot AKT1 and DICER1 mutations. Targeted transcriptome sequencing revealed recurrent TERT rearrangements (13%) involving partners CLPTM1L or DROSHA, and differential gene expression analysis showed FGFR1 upregulation in the TERT non-rearranged JGCTs under direct promoter control. Genome-wide DNA methylation rendered a clear delineation between AGCTs and JGCTs at the epigenomic level, further supporting its diagnostic utility in distinguishing among these tumors. Conclusions: This is the largest comprehensive molecular study of JGCTs, where we further expand our current understanding of JGCT pathogenesis and demonstrate putative oncogenic drivers and TERT rearrangements in a subset of tumors. Our findings further offer insights into possible targeted therapies in a rare entity.
Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome
Authors: Bernhard Gentner, Francesca Tucci, Stefania Galimberti, Francesca Fumagalli, Maurizio De Pellegrin, Paolo Silvani, Chiara Camesasca, Silvia Pontesilli, Silvia Darin, Francesca Ciotti, Marina Sarzana, Giulia Consiglieri, Chiara Filisetti, Giulia Forni, Laura Passerini, Daniela Tomasoni, Daniela Cesana, Andrea Calabria, Giulio Spinozzi, Maria-Pia Cicalese, Valeria Calbi, Maddalena Migliavacca, Federica Barzaghi, Francesca Ferrua, Vera Gallo, Simona Miglietta, Erika Zonari, Patali S. Cheruku, Claudia Forni, Marcella Facchini, Ambra Corti, Michela Gabaldo, Stefano Zancan, Serena Gasperini, Attilio Rovelli, Jaap-Jan Boelens, Simon A. Jones, Robert Wynn, Cristina Baldoli, Eugenio Montini, Silvia Gregori, Fabio Ciceri, Maria G. Valsecchi, Giancarlo la Marca, Rossella Parini, Luigi Naldini, Alessandro Aiuti, Maria-Ester Bernardo
Journal: New England Journal of Medicine (2021)

Allogeneic hematopoietic stem-cell transplantation is the standard of care for Hurler syndrome (mucopolysaccharidosis type I, Hurler variant [MPSIH]). However, this treatment is only partially curative and is associated with complications.
Abstract 054: Hypertension Treatment And Control In A New York City Healthcare System
Authors: Ayana K April-Sanders, Ladan Golestaneh, Lili Zhang, Katrina Swett, Paul Meissner, Eran Y Bellin, Carlos Rodriguez
Journal: Circulation (2022)

Background: We investigated the prevalence of and patient characteristics correlated with hypertension control in the Montefiore Health System, a large and predominantly minority healthcare system with locations in New York City and Southern portion of Upstate New York. Methods: Using outpatient care data, we included all individuals with hypertension defined by ICD 9/10 codes during 2018. Treatment and control status were defined by the presence of prescribed antihypertensive medication(s) and measured blood pressure (BP): Joint National Commission (JNC) criteria - &lt; 140 / 90 mmHg; or American Heart Association/American College of Cardiology (AHA/ACC) criteria - &lt;130 / 80 mmHg. We report the distribution of hypertension treatment and control by age, sex, and race/ethnicity. Results: Among 74,487 hypertensive patients [mean age 62 years ±14), 62% female, predominantly Black (42%) and Hispanic (41%), and low SES (-2.91 ±2.90)], 57% were treated, of which 57% had achieved BP control by JNC criteria and 23% by AHA/ACC criteria. Compared with untreated patients, those prescribed treatments were older (61%), more likely to be NH Black or Hispanic (60%), and report one or more comorbidities (76%) (all p&lt;0.0001). Prevalence of BP control by JNC criteria was lowest for NH Black (53%, p&lt;0.0001) and Hispanic (58%, p&lt;0.0001) patients than NH White and Asian (64%), and highest in patients ≥60 years (63%, p&lt;0.0001) and those with comorbidities (89%, p=0.002). Similar discrepancies were apparent at the 130/80 mmHg threshold. BP control characteristics did not vary by sex. Conclusions: Hypertension treatment and control rates in a large, urban health system were significantly lower than reported national averages. Overall, NH Whites had a lower likelihood of hypertension treatment; NH Black and Hispanic patients had significantly lower prevalence of control compared with other racial/ethnic groups, despite having higher treatment rates. Disparities in BP control by patient characteristics was heightened with the AHA/ACC criteria.
DOTATATE Uptake in an Axillary Lymph Node After COVID-19 Vaccination
Authors: James Brophy, Gregory Henkle, Eric M. Rohren
Journal: Clinical Nuclear Medicine (2021)

A 58-year-old man underwent DOTATATE PET/CT scan for follow-up of pulmonary neuroendocrine tumor after resection and adjuvant chemotherapy. On screening paperwork, the patient indicated having received the Johnson & Johnson/Janssen COVID-19 vaccine (Janssen Biotech, Inc) 1 day previously, administered in the right deltoid muscle. Reactive changes in regional lymph nodes is a known response for all 3 currently Food and Drug Administration-approved COVID-19 vaccines. Recent published data have demonstrated FDG PET-avid axillary lymphadenopathy subsequent to COVID-19 vaccination, and included here is a report of DOTATATE PET-avid axillary lymph node after injection of the Johnson & Johnson COVID-19 vaccine.
Correction: Enhanced Lipid Accumulation and Metabolism Are Required for the Differentiation and Activation of Tumor-Associated Macrophages
Authors: Pan Su, Qiang Wang, Enguang Bi, Xingzhe Ma, Lintao Liu, Maojie Yang, Jianfei Qian, Qing Yi
Journal: Cancer Research (2022)

In the original version of this article (1), there are errors in Fig. 7B and F. Specifically, in Fig. 7B, the groups were mislabeled; the red line represents the CD36+/+ group, and the black line represents the CD36−/− group. In Fig. 7F, the vertical axis label should be “IgG2b (mg/mL).” The correct images were provided, and the errors have been corrected in the latest online HTML and PDF version of the article. The authors regret these errors.
Characterization of Neurological Complications Among Children with Sickle Cell Disease in the United States: Findings from the 2007-2018 National Health Interview Survey (NHIS)
Authors: Joyce Gyamfi, Justin Tyler Lee, Farha Islam, Jumoke Opeyemi, Siphra Tampubolon, Temitope Ojo, Yuki Qiao, Andi Mai, Dorice Vieira, Emmanuel Peprah
Journal: Blood (2021)
A Case of Cystic Intrahepatic Cholangiocarcinoma Mimicking a Cyst
Authors: Chun-Meng Chen, Jianqiang Wang, Chun-Xiao Cao, Min Chen, Bin Huang
Journal: Clinical Nuclear Medicine (2022)

Intrahepatic cholangiocarcinoma (ICC) classically presents as irregular soft tissue lesions. Very rarely, ICC may manifest as a predominantly cystic mass. Here, we describe a 59-year-old man who was referred to the hospital due to abdominal pain. The presentation was highly suggestive of a hepatic cyst based on MRI. 18F-FDG PET/CT could not exclude a malignant hepatic tumor due to the high metabolism in the margin. Subsequently, the patient underwent a left hemihepatectomy. Histopathology revealed malignant ICC.
Estimation of Cross-Species Introgression Rates Using Genomic Data Despite Model Unidentifiability
Authors: Ziheng Yang, Tomáš Flouri
Journal: Molecular Biology and Evolution (2022)

Abstract Full-likelihood implementations of the multispecies coalescent with introgression (MSci) model treat genealogical fluctuations across the genome as a major source of information to infer the history of species divergence and gene flow using multilocus sequence data. However, MSci models are known to have unidentifiability issues, whereby different models or parameters make the same predictions about the data and cannot be distinguished by the data. Previous studies of unidentifiability have focused on heuristic methods based on gene trees and do not make an efficient use of the information in the data. Here we study the unidentifiability of MSci models under the full-likelihood methods. We characterize the unidentifiability of the bidirectional introgression (BDI) model, which assumes that gene flow occurs in both directions. We derive simple rules for arbitrary BDI models, which create unidentifiability of the label-switching type. In general, an MSci model with k BDI events has 2k unidentifiable modes or towers in the posterior, with each BDI event between sister species creating within-model parameter unidentifiability and each BDI event between nonsister species creating between-model unidentifiability. We develop novel algorithms for processing Markov chain Monte Carlo samples to remove label-switching problems and implement them in the bpp program. We analyze real and synthetic data to illustrate the utility of the BDI models and the new algorithms. We discuss the unidentifiability of heuristic methods and provide guidelines for the use of MSci models to infer gene flow using genomic data.
84P SHR-1316 vs placebo in combination with chemotherapy as perioperative treatment in patients with resectable stage II-III NSCLC: A randomized, double-blind, multicenter, phase Ib/III trial
Authors: Y-L. Wu, K. Chen, W. Xing, Q. Chen, L. Liu, Q. Zhang, D. Ge, Y-H. Liu, X. Lin, L. Wang, Y. Huang, W-Z. Zhong
Journal: Annals of Oncology (2022)
IL15 and Anti–PD-1 Augment the Efficacy of Agonistic Intratumoral Anti-CD40 in a Mouse Model with Multiple TRAMP-C2 Tumors
Authors: Wei Chen, Richard N. Bamford, Elijah F. Edmondson, Thomas A. Waldmann
Journal: Clinical Cancer Research (2022)

IL15 promotes activation and maintenance of natural killer (NK) and CD8+ T effector memory cells making it a potential immunotherapeutic agent for the treatment of cancer. However, monotherapy with IL15 was ineffective in patients with cancer, indicating that it would have to be used in combination with other anticancer agents. The administration of high doses of common gamma chain cytokines, such as IL15, is associated with the generation of "helpless" antigen-nonspecific CD8 T cells. The generation of the tumor-specific cytotoxic T cells can be mediated by CD40 signaling via agonistic anti-CD40 antibodies. Nevertheless, parenteral administration of anti-CD40 antibodies is associated with unacceptable side effects, such as thrombocytopenia and hepatic toxicity, which can be avoided by intratumoral administration.We investigated the combination of IL15 with an intratumoral anti-CD40 monoclonal antibody (mAb) in a dual tumor TRAMP-C2 murine prostate cancer model and expanded the regimen to include an anti-PD-1 mAb.Here we demonstrated that anti-CD40 given intratumorally not only showed significant antitumor activity in treated tumors, but also noninjected contralateral tumors, indicative of abscopal efficacy. The combination of IL15 with intratumoral anti-CD40 showed an additive immune response with an increase in the number of tumor-specific tetramer-positive CD8 T cells. Furthermore, the addition of anti-PD-1 further improved efficacy mediated by the anti-CD40/IL15 combination.These studies support the initiation of a clinical trial in patients with cancer using IL15 in association with the checkpoint inhibitor, anti-PD-1, and intratumoral optimized anti-CD40.
Genomic sequencing for bladder urothelial carcinoma and its clinical implications for immunotherapy.
Authors: Ryul Kim, Jeeyun Lee, Ghee Young Kwon, Jung Yong Hong, Byong Chang Jeong, Se Hoon Park
Journal: Journal of Clinical Oncology (2022)

551 Background: To explore the genomic and transcriptomic landscape of bladder cancer (BC) and its implication for treatment with an immune checkpoint inhibitor (ICI). Methods: We analyzed whole-exome and -transcriptome sequences of tumor samples from 64 BC patients who underwent surgical resection with either transurethral resection or radical cystectomy. For exploratory purposes, PD-L1 expression was evaluated in a subset of patients (n = 57) including those treated with ICI (n = 8). Results: We identified frequent molecular dysregulations in chromatin regulatory genes ( KDM6A, ARID1A, MLL2, and STAG2) and recurrent copy number alterations. Thirty-five samples (54.7%) were PD-L1-positive (PD-L1 combined positive score ≥ 1) with a significantly higher exonic tumor mutational burden (TMB) compared to PD-L1-negative BC samples ( P= 0.010). We observed that various immune-responsive pathways, including the PD-L1 signaling pathway, were enriched significantly in PD-L1-positive BCs. Interestingly, genes in the CTLA4 pathway were enriched significantly in PD-L1-positive BC as well. Among 8 patients who received ICI, progressive disease was confirmed in one patient, whose tumor had low exonic TMB, negative PD-L1 status, and a relatively colder microenvironment. Conclusions: Gaining new insights into the molecular landscape of BC will improve treatment strategies. Our analysis suggests a rationale for studying dual checkpoint inhibition against BC.
Abstract P218: Analysis Of YouTube Videos As A Patient-Education Tool For Cardiac Stress Testing
Authors: Sanjana Janumpally, Sai Kamma, Bradley Nus, Kylie Wu, Trey Sledge, Grant Torres, Yasser Sammour
Journal: Circulation (2022)

Background: YouTube is the most popular video sharing platform, and it is a common source of information for people interested in learning about medical topics. YouTube videos discussing cardiac stress testing have amassed millions of views, but their educational quality has not been thoroughly assessed. We sought to investigate the quality of cardiac stress testing videos on YouTube. Methods: We searched YouTube.com for keywords including “Cardiac Stress Test” and “Exercise Stress Test”. We evaluated 113 videos with at least 15,000 views and excluded 51 videos. The exclusion criteria comprised videos that were unrelated, under 1 minute, not in English, or repeats of a video. The remaining videos were rated by two independent reviewers using the Global Quality Scale (GQS; 4-5 = high quality, 1-3 = low quality), to evaluate usefulness. The view count, modality, upload source and date were used for additional sub-analyses to determine possible associations with the educational quality of videos. Modalities that were analyzed included patient-friendly delivery methods such as patients speaking about their experiences or interviews with patients on their experiences, live patient tests where the patient undergoes cardiac stress testing to educate viewers, or physician-led presentations. Results: The average GQS score was 5 in 4 out of 62 videos (4/62; 6.5%), 4 in 14 videos (14/62; 22.5%), and 0-3 in 44 videos (44/62; 71%) with a mean overall GQS score of 3.04 demonstrating moderate-suboptimal educational quality of videos. Days since upload and view ratio were not associated with educational quality of the videos. Physician-uploaded videos (37/62; 60%) had significantly higher GQS scores compared with non-physicians (3.43 vs. 2.46; p&lt;0.01). When grouped by modality, live patient tests (23/62; 37%) had the highest GQS score of 3.33 while physician-led presentations (28/62; 45%) produced GQS score of 3.13. Patient-friendly delivery methods (interviews and patient stories) (11/62; 18%) had the lowest average GQS score of 2.23. Conclusion: There is an abundance of content about cardiac stress testing on YouTube videos that often deliver low quality information. Healthcare providers need to be cognizant about possible misinformation their patients may encounter. YouTube can be a useful resource for physicians and patients in the future as shared decision-making aids if higher quality videos are uploaded directly by physicians.
Abstract 10808: Prognostic Significance of Obstructive Coronary Artery Disease in Patients Admitted with Acute Decompensated Heart Failure: The ARIC Study Community Surveillance
Authors: Zainali Chunawala, Arman Qamar, Sameer Arora, Ambarish Pandey, Marat Fudim, Muthiah Vaduganathan, Robert J Mentz, Melissa Caughey
Journal: Circulation (2021)

Background: Coronary artery disease (CAD) is a common cause of heart failure (HF). Whether the extent of coronary artery stenosis differs by HF type or prognosis for patients admitted with acute decompensated heart failure (ADHF) is uncertain. Methods: The Atherosclerosis Risk in Communities (ARIC) study conducted hospital surveillance of adjudicated HF in 4 US areas from 2005-2014. Medical histories were abstracted from the hospital record. Obstructive CAD was defined as &gt; 49% stenosis in the left main coronary artery or &gt;74% stenosis in the other major coronary arteries. Associations between obstructive CAD and 28-day mortality were analyzed separately for heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF), adjusting for age, race, sex, year of admission, and coronary revascularization procedures. All analyses were weighted by the inverse of the sampling probability. Results: A total of 5115 patients admitted with ADHF underwent coronary angiography during the hospital visit (mean age = 72, 45% women, 28% Black, 30% HFpEF). Obstructive CAD was more prevalent with HFrEF ( Figure 1 ), whether at the left main coronary artery (16% vs 12%), left anterior descending artery (50% vs 35%), left circumflex artery (42% vs 34%), right coronary artery (45% vs 34%), or multiple coronary vessels (47% vs 34%). A similar proportion of patients with obstructive CAD underwent revascularization, irrespective of HF type (HFrEF: 55%, HFpEF: 61%). After adjustments, obstructive CAD (in any vessel) was associated with higher 28-day mortality, both for HFrEF (OR: 3.21; CI: 1.91 - 5.97) and HFpEF (OR: 3.62; 95% CI: 1.43 - 9.18) with no significant interaction by HF type ( P -interaction = 0.9). Conclusion: Patients hospitalized with ADHF and coexisting obstructive CAD are at greater risk of short-term mortality, irrespective of the HF type, warranting the need for effective interventions as well as secondary preventive measures in this population.
Multifaceted Spatial and Functional Zonation of Cardiac Cells in Adult Human Heart
Authors: Liang Chen, Kui Hua, Ningning Zhang, Jingyu Wang, Jian Meng, Zhenliang Hu, Haoxiang Gao, Fanhong Li, Yang Chen, Jie Ren, Liyang Liu, Qiming Zhou, Jin Gu, Jiangping Song, Xuegong Zhang, Shengshou Hu
Journal: Circulation (2022)