tbuckley/cabot-search huggingface dataset:
Trends in Human Papillomavirus–Associated Cancers, Demographic Characteristics, and Vaccinations in the US, 2001-2017
Authors: Cheng-I. Liao, Alex Andrea Francoeur, Daniel S. Kapp, Michelle Ann P. Caesar, Warner K. Huh, John K. Chan
Journal: JAMA Network Open (2022)

Nearly 45 000 human papillomavirus (HPV)-associated cancers are diagnosed annually in the US. The HPV vaccine has been approved since 2006, but information on the association between vaccination and the incidence of HPV-attributable cancers is unclear.To evaluate the potential association of screening and vaccination on the trends of HPV-associated cancers.A retrospective, population-based cross-sectional study was conducted using data on HPV-associated (oropharyngeal squamous cell carcinoma [SCC], anal/rectal SCC, vulvar SCC, vaginal SCC, cervical carcinoma, and penile SCC) cancers from the US Cancer Statistics Public Use Database, representing 99% of the US population, between January 1, 2001, and December 31, 2017; HPV vaccination and screening data from the Behavioral Risk Factor Surveillance between January 1, 2001, and December 31, 2016; and TeenVaxView between January 1, 2008, and December 31, 2018. National Cancer Database and Behavioral Risk Factor Surveillance were used to correct for hysterectomy. Data analysis was performed from April 1, 2020, to June 30, 2021.Patient demographic characteristics, including age, race and ethnicity, sex, region, and vaccination status.The main outcomes examined in this study were diagnoses of any HPV-associated cancer and HPV vaccination status.A total of 657 317 HPV-associated cancers (exact ages not collected by the United States Cancer Statistics); of these, 264 019 (40.2%) developed in men and 393 298 (59.8%) in women; 14 520 individuals (2.2%) were non-Hispanic Asian/Pacific Islander, 74 641 (11.4%) were non-Hispanic Black, 59 841 (9.1%) were Hispanic, and 499 899 were non-Hispanic White (76.1%). More than half (206 075 [52.4%]) of cancers in women were cervical, whereas most (211 421 [80.1%]) cancers in men were oropharyngeal. In female adolescents (aged 13-17 years), the vaccination rate increased from 37.2% to 69.9% from 2008 to 2018 (annual percent change: 6.57% [95% CI, 5.83%-7.32%]). Before vaccination approval, cervical cancer rates in the 20- to 24-year age group were decreasing at 2.29% annually (P = .045); after vaccine approval, this rate has been decreasing at 9.50% (P = .003). In men, annual increases were noted in oropharyngeal (2.71%) and anal/rectal (1.83%) cancers (P < .001); in women, the incidence of oropharyngeal remained stable but anal/rectal cancer increased at 2.83% every year (P < .001).In the US, cervical cancer rates have decreased at a population level, especially in younger women. The findings of this study suggest this decrease may be associated with vaccination. Given the increase in oropharyngeal and anal/rectal cancers, particularly in men, it may be important to highlight vaccination uptake in both sexes.
CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION AND LONG-TERM MORTALITY AFTER FIRST-TIME VENOUS THROMBOEMBOLISM: A POPULATION-BASED COHORT STUDY
Authors: Kasper Bonnesen, Mads J. Andersen, Asger Andersen, Jens E. Nielsen-Kudsk, Søren Mellemkjær, Frederikus A. Klok, Henrik T. Sørensen, Morten Schmidt
Journal: Journal of the American College of Cardiology (2022)
6MO Translational relevance of the combined treatment PARP inhibitors and AsiDNA in homologous recombination proficient tumors
Authors: W. Jdey, V. Trochon-Joseph, C. Doizelet, V. Hayes, A. Cohendet, M-C. Lienafa, C. Zandanel, O. De Beaumont, J. Miara
Journal: Annals of Oncology (2022)
Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats
Authors: Justin C. Burrell, Suradip Das, Franco A. Laimo, Kritika S. Katiyar, Kevin D. Browne, Robert B. Shultz, Vishal J. Tien, Phuong T. Vu, Dmitriy Petrov, Zarina S. Ali, Joseph M. Rosen, D. Kacy Cullen
Journal: Bioactive Materials (2022)
Effect of Coronary Arterial Dominance Post Primary Percutaneous Coronary Artery Intervention (PCI) during Hospital Stay and at 3-Month Follow-up
Authors: Abd Rabou Hamed, Ahmed Elkersh, Ahmed Hegab, Abdulaziz Aboshahba
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

Background: Coronary vessel dominance, defined by the coronary artery that supplies the posterior descending artery (PDA) and posterolateral branches, influences the relative contribution of the different coronary arteries to the total left ventricular blood flow. This work aimed to evaluate the prognostic value of coronary arterial dominance post primary PCI, during hospital stay and at 3-month follow-up, which include; cardiac mortality, heart failure, non-fatal myocardial infarction, re-vascularization, stroke/TIA and re-admission for ACS. Methods: This prospective observational study included 100 patients a with STEMI who underwent successful primary percutaneous coronary intervention with TIMI III flow and without procedural complications. Patients were divided into 3 groups according to coronary dominance: Right coronary dominant group (RCD), left coronary dominant group (LCD) and balanced coronary dominant group (BCD). All patients were subjected to transthoracic echocardiogram and coronary angiography and Primary percutaneous coronary intervention. Results: Ticagrelor and clopidogrel during hospital stay and on hospital discharge were significantly used more with RCA group than LCX group and LCX &amp; RCA group (P=0.021, 0.012), (P=0.018, 0.014), respectively. GPIIB/IIIA was significantly more used during hospital stay with RCA group than LCX group and LCX &amp; RCA group(P=0.014). Nitrates was significantly used more on hospital discharge with RCA group than LCX group and LCX &amp; RCA group (P&lt;0.001). Conclusions: Coronary arterial domi¬nance showed significant prognostic value in cases of myocardial Infarction after PCI, heart failure in LCX cases and in revascularization, heart failure, and stroke/TIA cases in RCA. Further, readmission for ACS was the most common outcome in all groups after 3-months follow-up.
Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2
Authors: Kathryn E. Kistler, John Huddleston, Trevor Bedford
Journal: Cell Host & Microbe (2022)

The SARS-CoV-2 pandemic has resulted in numerous virus variants, some of which have altered receptor-binding or antigenic phenotypes. Here, we quantify the degree to which adaptive evolution is driving the accumulation of mutations across the genome. We correlate clade growth with mutation accumulation, compare rates of nonsynonymous to synonymous divergence, assess temporal clustering of mutations, and evaluate the evolutionary success of individual mutations. We find that spike S1 is the focus of adaptive evolution but also identify positively selected mutations in other proteins (notably Nsp6) that are sculpting the evolutionary trajectory of SARS-CoV-2. Adaptive changes in S1 accumulated rapidly, resulting in a remarkably high ratio of nonsynonymous to synonymous divergence that is 2.5× greater than that observed in influenza hemagglutinin HA1 at the beginning of the 2009 H1N1 pandemic. These findings uncover a high degree of adaptation in S1 and suggest that SARS-CoV-2 might undergo antigenic drift.
USING EXPLAINABLE ARTIFICIAL INTELLIGENCE TO PREDICT LETHAL OUTCOMES IN PATIENTS WITH MYOCARDIAL INFARCTION BASED ON ELECTROCARDIOGRAPHIC AND CLINICAL DATA
Authors: Varun Bhasin, Raj Dalsania, Bobby Ghosh, Ashok Chaudhary, Deepa Balasubramanian Iyer, Naveena Yanamala, Partho P. Sengupta
Journal: Journal of the American College of Cardiology (2022)
BPI22-015: Analysis of NCCN-Preferred Treatment Regimen Ordering via an EHR-Embedded Decision Support Tool in a Community Oncology Practice
Authors: Jonas M Congelli, Rebecca Maniago, Stephanie Jou, Janet Donegan, Ivy Altomare
Journal: Journal of the National Comprehensive Cancer Network (2022)

"BPI22-015: Analysis of NCCN-Preferred Treatment Regimen Ordering via an EHR-Embedded Decision Support Tool in a Community Oncology Practice" published on 31 Mar 2022 by National Comprehensive Cancer Network.
IMPACT OF ALTERED RIGHT VENTRICULAR-PULMONARY ARTERY COUPLING BY EXERCISE ON EXERCISE CAPACITY IN HFPEF PATIENTS WITHOUT LEFT VENTRICULAR STRUCTURAL ABNORMALITY
Authors: Suguru Ishizaka, Hiroyuki Iwano, Shingo Tsujinaga, Michito Murayama, Hiroyuki Aoyagi, Yoji Tamaki, Ko Motoi, Yasuyuki Chiba, Masahiro Nakabachi, Takuma Sato, Kiwamu Kamiya, Sanae Kaga, Toshiyuki Nagai, Toshihisa Anzai
Journal: Journal of the American College of Cardiology (2022)
Systemic and single cell level responses to 1 nm size biomaterials demonstrate distinct biological effects revealed by multi-omics atlas
Authors: Tao Zhang, Tingyun Lei, Ruojin Yan, Bo Zhou, Chunmei Fan, Yanyan Zhao, Shasha Yao, Haihua Pan, Yangwu Chen, Bingbing Wu, Yuwei Yang, Lijuan Hu, Shen Gu, Xiaoyi Chen, Fangyuan Bao, Yu Li, Hanqi Xie, Ruikang Tang, Xiao Chen, Zi Yin
Journal: Bioactive Materials (2022)

Although ultra-small nanoclusters (USNCs, < 2 nm) have immense application capabilities in biomedicine, the investigation on body-wide organ responses towards USNCs is scant. Here, applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues, we systematically evaluate the interactions between the host and calcium phosphate (CaP) USNCs at the organism level. Combining single-cell mass cytometry, and magnetic luminex assay results, we identify dynamic immune responses to CaP USNCs at the single cell resolution. The innate immune is initially activated and followed by adaptive immune activation, as evidenced by dynamic immune cells proportions. Furthermore, using Nano Genome Atlas of multi-tissues, we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney. Moreover, based on the immunological response profiles, histological evaluation of major organs and local tissue, and a body-wide transcriptomics, we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection. Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.
CONGESTIVE HEART FAILURE AS A PRESENTATION OF ACUTE MYELOID LEUKEMIA IN A YOUNG PATIENT
Authors: Emadeldeen Elgwairi, Amira Abdalla, Mostafa Abohelwa, Zeyad Elharabi, Gaspar Del Rio-Pertuz, Kanak Parmar, Marina Iskandir
Journal: Journal of the American College of Cardiology (2022)
A REAL-WORD, PROSPECTIVE OBSERVATIONAL STUDY TO COMPARE RIVAROXABAN VERSUS VITAMIN K ANTAGONIST TREATMENT IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION AND ADVANCED CHRONIC KIDNEY DISEASE
Authors: Reinhold Hugo Kreutz, Gilbert Deray, Juergen Floege, Marianne Gwechenberger, Kai Hahn, Andreas Luft, Pontus Persson, Jan Beyer-Westendorf
Journal: Journal of the American College of Cardiology (2022)
Joint patient and clinician priority setting to identify 10 key research questions regarding the long-term sequelae of COVID-19
Authors: Linzy Houchen-Wolloff, Krisnah Poinasamy, Kate Holmes, Maryrose Tarpey, Claire Hastie, Kelly Raihani, Natalie Rogers, Nikki Smith, Dawn Adams, Paul Burgess, Jean Clark, Clare Cranage, Mahadev Desai, Nicola Geary, Rhyan Gill, Jitendra Mangwani, Lily Staunton, Colin Berry, Charlotte E Bolton, Trudie Chalder, James Chalmers, Anthony De Soyza, Omer Elneima, John Geddes, Simon Heller, Ling-Pei Ho, Joseph Jacob, Hamish McAuley, Aarti Parmar, Jennifer K Quint, Betty Raman, Matthew Rowland, Amisha Singapuri, Sally J Singh, David Thomas, Mark R Toshner, Louise V Wain, Alex Robert Horsley, Michael Marks, Christopher E Brightling, Rachael A Evans
Journal: Thorax (2022)

Given the large numbers of people infected and high rates of ongoing morbidity, research is clearly required to address the needs of adult survivors of COVID-19 living with ongoing symptoms (long COVID). To help direct resource and research efforts, we completed a research prioritisation process incorporating views from adults with ongoing symptoms of COVID-19, carers, clinicians and clinical researchers. The final top 10 research questions were agreed at an independently mediated workshop and included: identifying underlying mechanisms of long COVID, establishing diagnostic tools, understanding trajectory of recovery and evaluating the role of interventions both during the acute and persistent phases of the illness.
A Conversation About Suicide During Medical Training
Authors: Amole Khadilkar
Journal: JAMA Neurology (2022)

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A PI3Kγ mimetic peptide triggers CFTR gating, bronchodilation, and reduced inflammation in obstructive airway diseases
Authors: Alessandra Ghigo, Alessandra Murabito, Valentina Sala, Anna Rita Pisano, Serena Bertolini, Ambra Gianotti, Emanuela Caci, Alessio Montresor, Aiswarya Premchandar, Flora Pirozzi, Kai Ren, Angela Della Sala, Marco Mergiotti, Wito Richter, Eyleen de Poel, Michaela Matthey, Sara Caldrer, Rosa A. Cardone, Federica Civiletti, Andrea Costamagna, Nancy L. Quinney, Cosmin Butnarasu, Sonja Visentin, Maria Rosaria Ruggiero, Simona Baroni, Simonetta Geninatti Crich, Damien Ramel, Muriel Laffargue, Carlo G. Tocchetti, Renzo Levi, Marco Conti, Xiao-Yun Lu, Paola Melotti, Claudio Sorio, Virginia De Rose, Fabrizio Facchinetti, Vito Fanelli, Daniela Wenzel, Bernd K. Fleischmann, Marcus A. Mall, Jeffrey Beekman, Carlo Laudanna, Martina Gentzsch, Gergely L. Lukacs, Nicoletta Pedemonte, Emilio Hirsch
Journal: Science Translational Medicine (2022)

Cyclic adenosine 3′,5′-monophosphate (cAMP)–elevating agents, such as β 2 -adrenergic receptor (β 2 -AR) agonists and phosphodiesterase (PDE) inhibitors, remain a mainstay in the treatment of obstructive respiratory diseases, conditions characterized by airway constriction, inflammation, and mucus hypersecretion. However, their clinical use is limited by unwanted side effects because of unrestricted cAMP elevation in the airways and in distant organs. Here, we identified the A-kinase anchoring protein phosphoinositide 3-kinase γ (PI3Kγ) as a critical regulator of a discrete cAMP signaling microdomain activated by β 2 -ARs in airway structural and inflammatory cells. Displacement of the PI3Kγ-anchored pool of protein kinase A (PKA) by an inhaled, cell-permeable, PI3Kγ mimetic peptide (PI3Kγ MP) inhibited a pool of subcortical PDE4B and PDE4D and safely increased cAMP in the lungs, leading to airway smooth muscle relaxation and reduced neutrophil infiltration in a murine model of asthma. In human bronchial epithelial cells, PI3Kγ MP induced unexpected cAMP and PKA elevations restricted to the vicinity of the cystic fibrosis transmembrane conductance regulator (CFTR), the ion channel controlling mucus hydration that is mutated in cystic fibrosis (CF). PI3Kγ MP promoted the phosphorylation of wild-type CFTR on serine-737, triggering channel gating, and rescued the function of F508del-CFTR, the most prevalent CF mutant, by enhancing the effects of existing CFTR modulators. These results unveil PI3Kγ as the regulator of a β 2 -AR/cAMP microdomain central to smooth muscle contraction, immune cell activation, and epithelial fluid secretion in the airways, suggesting the use of a PI3Kγ MP for compartment-restricted, therapeutic cAMP elevation in chronic obstructive respiratory diseases.
Explaining the gradient: Requirements for theories of visual awareness
Authors: Thomas Schmidt, Melanie Biafora
Journal: Behavioral and Brain Sciences (2022)

Abstract We propose that any theory of visual awareness must explain the gradient of different awareness measures over experimental conditions, especially when those measures form double dissociations among each other. Theories meeting this requirement must be specific to the measured facets of awareness, such as motion, contrast, or color. Integrated information theory (IIT) lacks such specificity because it is an underconstrained theory with unspecific predictions.
Alternative RNA splicing defects in pediatric cancers: new insights in tumorigenesis and potential therapeutic vulnerabilities
Authors: A.S. Venkataramany, K.M. Schieffer, K. Lee, C.E. Cottrell, P.Y. Wang, E.R. Mardis, T.P. Cripe, D.S. Chandler
Journal: Annals of Oncology (2022)

Compared with adult cancers, pediatric cancers are uniquely characterized by a genomically stable landscape and lower tumor mutational burden. Alternative splicing, however, a global cellular process that produces different messenger RNA/protein isoforms from a single messenger RNA transcript, has been increasingly implicated in the development of pediatric cancers.We review the current literature on the role of alternative splicing in adult cancer, cancer predisposition syndromes, and pediatric cancers. We also describe multiple splice variants identified in adult cancers and confirmed through comprehensive genomic profiling in our institutional cohort of rare, refractory, and relapsed pediatric and adolescent young adult cancer patients. Finally, we summarize the contributions of alternative splicing events to neoantigens and chemoresistance and prospects for splicing-based therapies.Published dysregulated splicing events can be categorized as exon inclusion, exon exclusion, splicing factor up-regulation, or splice site alterations. We observe these phenomena in cancer predisposition syndromes (Lynch syndrome, Li-Fraumeni syndrome, CHEK2) and pediatric leukemia (B-cell acute lymphoblastic leukemia), sarcomas (Ewing sarcoma, rhabdomyosarcoma, osteosarcoma), retinoblastoma, Wilms' tumor, and neuroblastoma. Within our institutional cohort, we demonstrate splice variants in key regulatory genes (CHEK2, TP53, PIK3R1, MDM2, KDM6A, NF1) that resulted in exon exclusion or splice site alterations, which were predicted to impact functional protein expression and promote tumorigenesis. Differentially spliced isoforms and splicing proteins also impact neoantigen creation and treatment resistance, such as imatinib or glucocorticoid regimens. Additionally, splice-altering strategies with the potential to change the therapeutic landscape of pediatric cancers include antisense oligonucleotides, adeno-associated virus gene transfers, and small molecule inhibitors.Alternative splicing plays a critical role in the formation and growth of pediatric cancers, and our institutional cohort confirms and highlights the broad spectrum of affected genes in a variety of cancers. Further studies that elucidate the mechanisms of disease-inducing splicing events will contribute toward the development of novel therapeutics.
RISK STRATIFICATION OF POST-TAVR NEW LBBB OUTCOMES: INSIGHTS FROM A MULTICENTER INTERNATIONAL STUDY
Authors: Takahiro Tsushima, Anthony Main, Sadeer G. Al-Kindi, Luis Augusto Palma Dallan, Heather Wheat, Cristian Baeza, Marc Pelletier, Mauricio Arruda, Judith A. Mackall, Sergio Thal, Yohei Ohno, Kyong-Hee Lee, Dimytri A. Siqueira, Tsuyoshi Kaneko, Morgan Harloff, Giuliano Costa, Marco Barbanti, Guilherme Attizzani
Journal: Journal of the American College of Cardiology (2022)
Diagnosis of Primary Scrotal Lymphedema Using 99mTc-Sulfur Colloid Lymphoscintigram
Authors: Annie Rhee, Jonathan A. Flug, William J. Casey, Michael C. Roarke, Alanna M. Rebecca, Ming Yang
Journal: Clinical Nuclear Medicine (2022)

We report a case of a 19-year-old man who presented with severe scrotal swelling. His medical history was notable for severe global edema at birth. Most areas of swelling had resolved by adolescence with exception of the scrotum and the left lower extremity. 99mTc-filtered sulfur colloid lymphoscintigraphy of the lower extremities demonstrated prominent dermal backflow into the superficial scrotum and thighs, which were confirmed on the SPECT/CT images, and correlated with findings on MR lymphangiogram. Lymphoscintigram and MR lymphangiogram may provide complementary information to aid diagnosis and management of primary scrotal lymphedema.
EICOSAPENTAENOIC ACID (EPA) DECREASES ANGIOTENSIN CONVERTING ENZYME (ACE) EXPRESSION IN VASCULAR AND PULMONARY ENDOTHELIUM FOLLOWING CYTOKINE CHALLENGE
Authors: Samuel CR R. Sherratt, Peter Libby, Deepak L. Bhatt, Hazem Dawoud, Tadeusz Malinski, R. Preston Mason
Journal: Journal of the American College of Cardiology (2022)
Screening for Eating Disorders in Adolescents and Adults
Authors: Jill Jin
Journal: JAMA (2022)

Cynthia Feltner, MD, MPH; Christine Peat, PhD; Shivani Reddy, MD, MS; Sean Riley, MA, MSc; Nancy Berkman, PhD; Jennifer Cook Middleton, PhD; Casey Balio, PhD; Manny Coker-Schwimmer, MPH; Daniel E. Jonas, MD, MPH
SLC5A3-Dependent Myo-inositol Auxotrophy in Acute Myeloid Leukemia
Authors: Yiliang Wei, Yu-Han Huang, Damianos S. Skopelitis, Shruti V. Iyer, Ana S.H. Costa, Zhaolin Yang, Melissa Kramer, Emmalee R. Adelman, Olaf Klingbeil, Osama E. Demerdash, Sofya A. Polyanskaya, Kenneth Chang, Sara Goodwin, Emily Hodges, W. Richard McCombie, Maria E. Figueroa, Christopher R. Vakoc
Journal: Cancer Discovery (2021)

An enhanced requirement for nutrients is a hallmark property of cancer cells. Here, we optimized an in vivo genetic screening strategy in acute myeloid leukemia (AML), which led to the identification of the myo-inositol transporter SLC5A3 as a dependency in this disease. We demonstrate that SLC5A3 is essential to support a myo-inositol auxotrophy in AML. The commonality among SLC5A3-dependent AML lines is the transcriptional silencing of ISYNA1, which encodes the rate-limiting enzyme for myo-inositol biosynthesis, inositol-3-phosphate synthase 1. We use gain- and loss-of-function experiments to reveal a synthetic lethal genetic interaction between ISYNA1 and SLC5A3 in AML, which function redundantly to sustain intracellular myo-inositol. Transcriptional silencing and DNA hypermethylation of ISYNA1 occur in a recurrent manner in human AML patient samples, in association with IDH1/IDH2 and CEBPA mutations. Our findings reveal myo-inositol as a nutrient dependency in AML caused by the aberrant silencing of a biosynthetic enzyme. SIGNIFICANCE: We show how epigenetic silencing can provoke a nutrient dependency in AML by exploiting a synthetic lethality relationship between biosynthesis and transport of myo-inositol. Blocking the function of this solute carrier may have therapeutic potential in an epigenetically defined subset of AML.This article is highlighted in the In This Issue feature, p. 275.
LEFT VENTRICULAR END-DIASTOLIC PRESSURE IS ASSOCIATED WITH INCIDENT CONTRAST-INDUCED NEPHROPATHY AND CLINICAL OUTCOMES IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS INTERVENTION
Authors: Laura Hanson, Cheng Yee Goh, Sara Vogrin, Samer Noaman, Omar Al-Mukhtar, Daniel Schneider, Yik Cheng, Noah Wexler, Kawa Haji, Chris Neil, Dion Stub, Nicholas R. Cox, William Chan
Journal: Journal of the American College of Cardiology (2022)