tbuckley/cabot-search huggingface dataset:
P37.16 Alterations in HRR Related Genes as Potential Markers of Clinical Benefit from PARP Inhibitor and PD-1/PD-L1 Blockade in Advanced Lung Cancer
Authors: Y. Lei, G. An, B. Duan, Y. Liu, X. Wang, Y. Liu, L. Hou, Y. Hou, M. Yu, D. Li, Q. Wei, D. Gu, L. Chang, J. Bai
Journal: Journal of Thoracic Oncology (2021)
1737P National approaches to managing cancer care: Responses of countries in the MENA region to COVID-19 pandemic
Authors: Z. Benbrahim, M. Al Asiri, B. Al Bahrani, M.A.M.A. AlNassar, H.O. Al-Shamsi, A. Bounedjar, N. El Saghir, Z. Fahed, S. Khatib, O.M.R. Khorshid, S. Labidi, N. Mellas, L. Mula-Hussain, A. Saleh Hadi Saeed, A. Jazieh
Journal: Annals of Oncology (2020)
Reovirus-induced cell-mediated immunity for the treatment of multiple myeloma within the resistant bone marrow niche
Authors: Louise M E Müller, Gemma Migneco, Gina B Scott, Jenny Down, Sancha King, Basem Askar, Victoria Jennings, Babatunde Oyajobi, Karen Scott, Emma West, Christy Ralph, Adel Samson, Elizabeth J Ilett, Munitta Muthana, Matt Coffey, Alan Melcher, Christopher Parrish, Gordon Cook, Michelle Lawson, Fiona Errington-Mais
Journal: Journal for ImmunoTherapy of Cancer (2021)

Multiple myeloma (MM) remains an incurable disease and oncolytic viruses offer a well-tolerated addition to the therapeutic arsenal. Oncolytic reovirus has progressed to phase I clinical trials and its direct lytic potential has been extensively studied. However, to date, the role for reovirus-induced immunotherapy against MM, and the impact of the bone marrow (BM) niche, have not been reported. This study used human peripheral blood mononuclear cells from healthy donors and in vitro co-culture of MM cells and BM stromal cells to recapitulate the resistant BM niche. Additionally, the 5TGM1-Kalw/RijHSD immunocompetent in vivo model was used to examine reovirus efficacy and characterize reovirus-induced immune responses in the BM and spleen following intravenous administration. Collectively, these in vitro and in vivo models were used to characterize the development of innate and adaptive antimyeloma immunity following reovirus treatment. Using the 5TGM1-Kalw/RijHSD immunocompetent in vivo model we have demonstrated that reovirus reduces both MM tumor burden and myeloma-induced bone disease. Furthermore, detailed immune characterization revealed that reovirus: (i) increased natural killer (NK) cell and CD8+ T cell numbers; (ii) activated NK cells and CD8+ T cells and (iii) upregulated effector-memory CD8+ T cells. Moreover, increased effector-memory CD8+ T cells correlated with decreased tumor burden. Next, we explored the potential for reovirus-induced immunotherapy using human co-culture models to mimic the myeloma-supportive BM niche. MM cells co-cultured with BM stromal cells displayed resistance to reovirus-induced oncolysis and bystander cytokine-killing but remained susceptible to killing by reovirus-activated NK cells and MM-specific cytotoxic T lymphocytes. These data highlight the importance of reovirus-induced immunotherapy for targeting MM cells within the BM niche and suggest that combination with agents which boost antitumor immune responses should be a priority.
Screening for Hearing Loss in Older Adults
Authors: Cynthia Feltner, Ina F. Wallace, Christine E. Kistler, Manny Coker-Schwimmer, Daniel E. Jonas
Journal: JAMA (2021)

Hearing loss is common in older adults and associated with adverse health and social outcomes.To update the evidence review on screening for hearing loss in adults 50 years or older to inform the US Preventive Services Task Force.MEDLINE, Cochrane Library, EMBASE, and trial registries through January 17, 2020; references; and experts; literature surveillance through October 8, 2020.English-language studies of accuracy, screening, and interventions for screen-detected or newly detected hearing loss.Dual review of abstracts, full-text articles, and study quality. Meta-analysis of screening test accuracy studies.Quality of life and function, other health and social outcomes, test accuracy, and harms.Forty-one studies (N = 26 386) were included, 18 of which were new since the previous review. One trial enrolling US veterans (n = 2305) assessed the benefits of screening; there was no significant difference in the proportion of participants experiencing a minimum clinically important difference in hearing-related function at 1 year (36%-40% in the screened groups vs 36% in the nonscreened group). Thirty-four studies (n = 23 228) evaluated test accuracy. For detecting mild hearing loss (>20-25 dB), single-question screening had a pooled sensitivity of 66% (95% CI, 58%-73%) and a pooled specificity of 76% (95% CI, 68%-83%) (10 studies, n = 12 637); for detecting moderate hearing loss (>35-40 dB), pooled sensitivity was 80% (95% CI, 68%-88%) and pooled specificity was 74% (95% CI, 59%-85%) (6 studies, n = 8774). In 5 studies (n = 2820) on the Hearing Handicap Inventory for the Elderly-Screening to detect moderate hearing loss (>40 dB), pooled sensitivity was 68% (95% CI, 52%-81%) and pooled specificity was 78% (95% CI, 67%-86%). Six trials (n = 853) evaluated amplification vs control in populations with screen-detected or recently detected hearing loss over 6 weeks to 4 months. Five measured hearing-related function via the Hearing Handicap Inventory for the Elderly; only 3 that enrolled veterans (n = 684) found a significant difference considered to represent a minimal important difference (>18.7 points). Few trials reported on other eligible outcomes, and no studies reported on harms of screening or interventions.Several screening tests can adequately detect hearing loss in older adults; no studies reported on the harms of screening or treatment. Evidence showing benefit from hearing aids on hearing-related function among adults with screen-detected or newly detected hearing loss is limited to studies enrolling veterans.
Change in ejection fraction and <scp>long‐term</scp> mortality in adults referred for echocardiography
Authors: Geoff Strange, David Playford, Gregory M. Scalia, David S. Celermajer, David Prior, Jim Codde, Yih‐Kai Chan, Max K. Bulsara, Simon Stewart
Journal: European Journal of Heart Failure (2021)

We investigated long-term mortality associated with changes in left ventricular ejection fraction (LVEF) in a large, real-world patient cohort.A total of 117 275 adults (63 ± 16 years, 46% women) had LVEF quantified by the same method ≥6 months apart. This included 17 343 cases (66 ± 15 years, 48% women) being initially investigated for heart failure (HF). During 3.3 [interquartile range (IQR) 1.7-6.0] years from first to last echocardiogram, median change in LVEF was -1 (IQR -8 to +5) units from a baseline of 62% (IQR 54-69%). During subsequent 7.6 (IQR 4.3-10.1) years of follow-up, 11 397 (9.7%) and 34 101 (29.1%) cases died from cardiovascular disease and all causes, respectively. Actual 5-year, all-cause mortality increased from 12% to 29% among those with the smallest to the largest decrease in LVEF (from <5 units to >30 units); the adjusted risk of cardiovascular-related mortality increased two- to eightfold beyond a >10-unit decline in LVEF (vs. minimal change; P < 0.001 for all comparisons). Among those initially investigated for HF (32% with initial LVEF <50%), the adjusted hazard ratio for cardiovascular-related mortality ranged from 0.35 [95% confidence interval (CI) 0.28-0.49] to 4.21 (95% CI 3.30-5.22) for a >30-unit increase to >30-unit decline in LVEF (vs. minimal change; P < 0.001 for both comparisons). A distinctive, bi-directional plateau of improved vs. worsening mortality was evident around a final LVEF of 50% to 55%.These data, derived from a large, heterogeneous cohort of adults being followed up with echocardiography, suggest that modest LVEF changes (particularly around an LVEF of 50-55%) may be of clinical significance.
Association Between Anesthesiologist Volume and Short-term Outcomes in Complex Gastrointestinal Cancer Surgery
Authors: Julie Hallet, Angela Jerath, Alexis F. Turgeon, Daniel I. McIsaac, Antoine Eskander, Jesse Zuckerman, Victoria Zuk, Safa Sohail, Gail E. Darling, Christoffer Dharma, Natalie G. Coburn, Rinku Sutradhar
Journal: JAMA Surgery (2021)

Intraoperative anesthesiology care is crucial to high-quality surgical care. The clinical expertise and experience of anesthesiologists may decrease the risk of adverse outcomes.To examine the association between anesthesiologist volume and short-term postoperative outcomes for complex gastrointestinal (GI) cancer surgery.This population-based cohort study used administrative health care data sets from various data sources in Ontario, Canada. Adult patients who underwent esophagectomy, pancreatectomy, or hepatectomy for GI cancer from January 1, 2007, to December 31, 2018, were eligible. Patients with an invalid identification number, a duplicate surgery record, and missing primary anesthesiologist information were excluded.Primary anesthesiologist volume was defined as the annual number of procedures of interest (esophagectomy, pancreatectomy, and hepatectomy) supported by that anesthesiologist in the 2 years before the index surgery. Volume was dichotomized into low-volume and high-volume categories, with 75th percentile or 6 or more procedures per year selected as the cutoff point.The primary outcome was a composite of 90-day major morbidity (with a Clavien-Dindo classification grade 3-5) and readmission. Secondary outcomes were individual components of the primary outcome. The association between exposure and outcomes was examined using multivariable logistic regression models, accounting for potential confounders.Of the 8096 patients included, 5369 were men (66.3%) and the median (interquartile range [IQR]) age was 65 (57-72) years. Operations were supported by 842 anesthesiologists and performed by 186 surgeons, and the median (IQR) anesthesiologist volume was 3 (1.5-6) procedures per year. A total of 2166 patients (26.7%) received care from high-volume anesthesiologists. Primary outcome occurred in 36.3% of patients in the high-volume group and 45.7% of patients in the low-volume group. After adjustment, care by high-volume anesthesiologists was independently associated with lower odds of the primary outcome (adjusted odds ratio [aOR], 0.85; 95% CI, 0.76-0.94), major morbidity (aOR, 0.83; 95% CI, 0.75-0.91), unplanned intensive care unit admission (aOR, 0.84; 95% CI, 0.76-0.94), but not readmission (aOR, 0.87; 95% CI, 0.73-1.05) or mortality (aOR, 1.05; 95% CI, 0.84-1.31). E-values analysis indicated that an unmeasured variable would unlikely substantively change the observed risk estimates.This study found that, among adults who underwent complex gastrointestinal cancer surgery, those who received care from high-volume anesthesiologists had a lower risk of adverse postoperative outcomes compared with those who received care from low-volume anesthesiologists. These findings support organizing perioperative care to increase anesthesiologist volume to optimize patient outcomes.
Continuity of Care Matters in All Health Care Settings
Authors: James S. Goodwin
Journal: JAMA Network Open (2021)

Concern regarding declining continuity of medical care has been growing during the past 3 decades.Continuity of care has been threatened by an array of forces, including the decrease in primary care physicians, changes in health insurance, the growth of specialization, and the need to ensure easy and timely access to care. 1 Most of the initial focus on continuity of care was in outpatient settings.Outpatient continuity with a primary care physician has been linked to decreased emergency department use and hospitalizations, lower costs, and higher patient and physician satisfaction. 1ese findings contributed to a greater emphasis on team-based care and other chronic care management models.Another setting that has experienced declines in continuity is the transition from the community to the hospital and back to the community. 2By 2006, most hospitalized Medicare patients received no care from a physician who had previously provided care for them. 2 Several studies have found that such discontinuity is associated with higher postdischarge costs and readmission rates. 3ntinuity of care received in the hospital has declined as well.Recent studies have suggested that patients admitted for medical illness are likely to be cared for by more than 1 general internist during their stay. 4,5Such discontinuity seems driven by the growth in care by hospitalists and the fact that many hospitalists have work schedules that do not allow for continuity of care.Just as with outpatient medicine, we might expect that hospitalized patients who experience discontinuities in their care also have worse outcomes.That is the question posed in the study by
Author Correction: COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials
Authors: Aakash Desai, Justin F. Gainor, Aparna Hegde, Alison M. Schram, Giuseppe Curigliano, Sumanta Pal, Stephen V. Liu, Balazs Halmos, Roman Groisberg, Enrique Grande, Tomislav Dragovich, Marc Matrana, Neeraj Agarwal, Sant Chawla, Shumei Kato, Gilberto Morgan, Pashtoon M. Kasi, Benjamin Solomon, Herbert H. Loong, Haeseong Park, Toni K. Choueiri, Ishwaria M. Subbiah, Naveen Pemmaraju, Vivek Subbiah
Journal: Nature Reviews Clinical Oncology (2021)

A Correction to this paper has been published: https://doi.org/10.1038/s41571-021-00503-2.
Endoscopic necrosectomy using endobronchial ultrasonography and transnasal gastroscopy via the percutaneous route
Authors: Nozomi Okuno, Kazuo Hara, Shin Haba, Akira Miyano, Toshifumi Yanaidani, Daiki Fumihara, Masahiro Yoshida
Journal: Endoscopy (2021)

Severe acute pancreatitis often causes walled-off necrosis (WON). Despite recent reports of endoscopic transgastric necrosectomy using a lumen-apposing metal stent [1] [2], treatment strategies for WON remain challenging.
OA02.03 Pembrolizumab Plus Platinum Chemotherapy and Radiotherapy in Unresectable, Locally Advanced, Stage III NSCLC: KEYNOTE-799
Authors: M. Reck, K.h. Lee, N. Frost, D.M. Kowalski, V. Breder, T. Pollock, N. Reguart, B. Houghton, X. Quantin, S.m. Keller, H. Liu, B. Piperdi, S.K. Jabbour
Journal: Journal of Thoracic Oncology (2021)
Trajectories of Children's Executive Function After Traumatic Brain Injury
Authors: Heather T. Keenan, Amy E. Clark, Richard Holubkov, Charles S. Cox, Linda Ewing-Cobbs
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Executive functions are critical for school and social success. Although these functions are adversely affected by pediatric traumatic brain injury (TBI), recovery patterns are not well established. <h3>Objective</h3> To examine 3-year trajectories of selected children's executive functions after TBI. <h3>Design, Setting, and Participants</h3> This prospective cohort study was conducted from January 22, 2013, to September 30, 2015, with 3-year follow-up at the level I pediatric trauma centers Primary Children's Hospital in Salt Lake City, Utah and Children's Memorial Hermann Hospital in Houston, Texas. Study participants included children aged 2 to 15 years with TBI or orthopedic injury (OI) who were treated at the participating hospitals. Children were consecutively recruited and stratified by injury severity and age group. A total of 625 children consented and completed a baseline survey; 559 (89%) children completed at least 1 follow-up and composed the analysis cohort. It was hypothesized that recovery would differ by injury severity, age at injury, and sex. Data analyses were performed from June to October 2019. <h3>Main Outcomes and Measures</h3> Growth curve models examined the pattern of change in the Emotional Control, Inhibit, Working Memory, and Plan-Organize subscales of the Behavior Rating Inventory of Executive Function (BRIEF) or BRIEF-Preschool. For all BRIEF subscales, higher scores indicate worse symptoms, and a score of 65 or greater represents clinical impairment. <h3>Results</h3> A total of 559 children (mean [SD] age, 8.6 [4.4] years; 356 boys [64%], 328 non-Hispanic White children [59%]) were included in the study: 155 (28%) children had mild TBI, 162 (29%) had complicated mild or moderate TBI, 90 (16%) had severe TBI, and 152 (27%) had OI. Growth curve trajectories varied by BRIEF subscale and injury severity. Overall, children with TBI did not return to their preinjury baseline, with a stepwise worsening of each outcome at 36 months by TBI severity compared with OI. Among children with severe TBI, trajectories accelerated fastest, indicating increased problems, from injury to 12 months for the Emotional Control (9.0 points; 95% CI, 6.0-11.9 points), Inhibit (3.6 points; 95% CI, 1.6-5.6 points), and Working Memory (7.0 points; 95% CI, 4.1-9.9 points) subscales. Their trajectories plateaued, with a secondary acceleration before 36 months for the Emotional Control and Working Memory subscales. Children with mild TBI had worse 36-month scores on all subscales except Inhibit compared with OI. Recovery patterns were similar for boys and girls. <h3>Conclusions and Relevance</h3> In this longitudinal cohort study of children with TBI, trajectory analysis revealed that some children worsen after a recovery plateau, suggesting a need for longitudinal reassessment beyond 1 year postinjury.
Abstract 10241: In the Sugen/hypoxia Model of Murine Pulmonary Arterial Hypertension, While Absence of S100A1 Exacerbates Right Ventricular Dysfunction, RAGE Deficiency Confers Protection
Authors: James N Tsoporis, Krystyna Teichert-Kuliszewska, Jean-Francois Desjardins, Shehla Izhar, Thomas G Parker
Journal: Circulation (2019)

Introduction: Previously, we demonstrated that under basal conditions in vivo, S100A1 knockout mice (KO) exhibited an elevation in right ventricular systolic pressure (RVSP), accompanied by an incr...
Single-cell transcriptomic profiling provides insights into the toxic effects of Zearalenone exposure on primordial follicle assembly
Authors: Yu Tian, Ming-Yu Zhang, Ai-Hong Zhao, Li Kong, Jun-Jie Wang, Wei Shen, Lan Li
Journal: Theranostics (2021)

Rationale: Zearalenone (ZEN), a pollutant in our daily diet, seriously threatens the reproductive health of humans and animals. The primordial follicle (PF) assembly in the mouse occurs during the perinatal period, which determines the whole ovarian reserve in reproductive lifespan. In the current investigation, we administered ZEN orally to perinatal mice from 16.5 days post coitum (dpc) to postnatal day 3 (PD3), and single-cell RNA sequencing (scRNA-seq) was performed on PD0 and PD3 ovarian tissues in the offspring to check ZEN toxic to primordial follicle formation at the single cell level. Methods: Ovarian tissues (in vivo) were examined by single cell RNA sequencing analysis, Immunostaining, and Western blotting. Ovarian tissues (in vitro) were examined by qRT-PCR, Immunostaining, and Western blotting. Results: We found that ZEN exposure altered the developmental trajectory of both germ cells and granulosa cells. Furthermore, after establishing the cell-cell communication network between germ cells and granulosa cells, we found that this was perturbed by ZEN exposure, especially during the Hippo signaling pathway. Conclusions: This study showed that ZEN affected the status of germ cells and granulosa cells through the Hippo signaling pathway and blocked the assembly of PFs. This research contributes to our deeper understanding of the mechanisms of toxicity in different cell types and the disruption of normal intercellular signaling by ZEN exposure.
Early Evidence of the Effect of SARS-CoV-2 Vaccine at One Medical Center
Authors: William Daniel, Marc Nivet, John Warner, Daniel K. Podolsky
Journal: New England Journal of Medicine (2021)

Effect of SARS-CoV-2 Vaccine at a Medical Center With the rollout of mRNA SARS-CoV-2 vaccines under emergency use authorization, dramatic decreases in the incidence of SARS-CoV-2 infections were se...
Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers
Authors: Fazlur Rahman Talukdar, Sheila C. Soares Lima, Rita Khoueiry, Ruhina Shirin Laskar, Cyrille Cuenin, Bruna Pereira Sorroche, Anne-Claire Boisson, Behnoush Abedi-Ardekani, Christine Carreira, Diana Menya, Charles P. Dzamalala, Mathewos Assefa, Abraham Aseffa, Vera Miranda-Gonçalves, Carmen Jerónimo, Rui M. Henrique, Ramin Shakeri, Reza Malekzadeh, Nagla Gasmelseed, Mona Ellaithi, Nitin Gangane, Daniel R.S. Middleton, Florence Le Calvez-Kelm, Akram Ghantous, Maria Leon Roux, Joachim Schüz, Valerie McCormack, M. Iqbal Parker, Luis Felipe Ribeiro Pinto, Zdenko Herceg
Journal: Cancer Research (2021)

Abstract Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. Significance: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers.
P90.02 BRAF Mutation And Peridiagnosis Thromboembolic Events In Advanced NSCLC Patients
Authors: I. Aparicio Salcedo, B. Moron, M. García Pardo, Í. Martínez, M. Alva, M. Arregui, V. Tirado, None Galera, R.M. Alvarez, L. Ortega, A.J. Muñoz, A. Calles
Journal: Journal of Thoracic Oncology (2021)