tbuckley/cabot-search huggingface dataset:
Association Between Workplace Absenteeism and Alcohol Use Disorder From the National Survey on Drug Use and Health, 2015-2019
Authors: Ian C. Parsley, Ann Marie Dale, Sherri L. Fisher, Carrie M. Mintz, Sarah M. Hartz, Bradley A. Evanoff, Laura J. Bierut
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Alcohol use disorder (AUD) is common and associated with increased morbidity. The degree to which AUD currently factors into workplace absenteeism needs further characterization in the US. <h3>Objective</h3> To examine the association between AUD and workplace absenteeism in a nationally representative sample. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from a nationally representative sample of noninstitutionalized US residents from the 2015-2019 National Survey on Drug Use and Health to examine the association of AUD with workplace absenteeism. Eligible respondents were aged 18 years and older who reported full-time employment. Data were analyzed from March to September 2021. <h3>Main Outcomes and Measures</h3> Primary outcomes were markers of workplace absenteeism as defined by the number of days missed from work because of illness or injury and days skipped from work in the last 30 days. Descriptive statistics, prevalence ratios, and logistic regression analyses were performed to assess the association between AUD and absenteeism. <h3>Results</h3> A total of 110 701 adults aged 18 years and older reported current full-time employment (58 948 [53.2%] men, 51 753 [46.8%] women; 12 776 [11.5%] Black, 18 096 [16.3%] Hispanic, and 69 506 [62.8%] White respondents). Weighted prevalence of AUD in this sample of working adults was 9.3% (95% CI, 9.0%-9.5%); 6.2% (95% CI, 6.0%-6.4%) of respondents met criteria for mild AUD, 1.9% (95% CI, 1.7%-2.0%) for moderate AUD, and 1.2% (95% CI, 1.1%-1.3%) for severe AUD. Mean days missed from work annually increased in a stepwise fashion with increasing AUD severity (no AUD, 13.0 days; 95% CI, 12.7-13.2 days; mild AUD, 17.7 days; 95% CI, 16.4-19.1 days; moderate AUD, 23.6 days; 95% CI, 21.5-25.7 days; severe AUD, 32.3 days; 95% CI, 27.5-37.0 days). People with AUD represented 9.3% of the full-time workforce and contributed to 14.1% of total reported workplace absences. <h3>Conclusions and Relevance</h3> In this cross-sectional study, AUD was disproportionately associated with an increased prevalence of workplace absenteeism, with individuals with AUD contributing over 232 million missed workdays annually. These results provide economic incentive for increased investment in AUD prevention and treatment, both for employers and policy makers.
HSR22-128: Patient-Level Barriers to Surveillance for Hepatocellular Carcinoma Among Patients With Chronic Liver Disease From the Provider Perspective
Authors: Eliza Wright Beal, Leva Gorji, Jaclyn Volney, Lindsey Sova, Ann McAlearney, Allan Tsung
Journal: Journal of the National Comprehensive Cancer Network (2022)

"HSR22-128: Patient-Level Barriers to Surveillance for Hepatocellular Carcinoma Among Patients With Chronic Liver Disease From the Provider Perspective" published on 31 Mar 2022 by National Comprehensive Cancer Network.
MYOCARDIAL INJURY AFTER IBRUTINIB INITIATION FOR HEMATOLOGIC MALIGNANCIES
Authors: Benjamin Buck, Aaron Chum, Mitkumar Patel, Rebecca R. Carter, Haseeb Nawaz, Vedat Yildiz, Patrick Ruiz, Tracy Wiczer, Kerry Rogers, Farrukh Awan, Seema Bhat, Avirup Guha, Adam Kittai, Orlando P. Simonetti, Subha V. Raman, Grant Wallace, Reynaldo Sanchez, Janice Bonsu, John A. Gambril, Devin Haddad, James Mann, Lai Wei, John Byrd, Jennifer Woyach, Daniel Addison
Journal: Journal of the American College of Cardiology (2022)
ASSOCIATION BETWEEN PULMONARY HYPERTENSION AND ITS EFFECT ON 30 DAY MORTALITY, READMISSION AND COST AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT, A MULTICENTER STUDY
Authors: Mansoor Ahmad, Juan Del Cid Fratti, Mena Henien, Pablo Barzallo, Daniel Whorf, Matthew Kerr, Brett Austin, Tiaranesha Jackson, Minchul Kim, Marco A. Barzallo, Sudhir Mungee
Journal: Journal of the American College of Cardiology (2022)
HSR22-182: Real-World Treatment Patterns Among Patients With Sézary Syndrome in the United States Between 2018 and 2020
Authors: Yang Zhao, Jackson Tang, Huanxue Zhou, Fiona Herr, Takeshi Takehashi, Takanobu Nomura, Eslie Dennis, Oleg Akilov
Journal: Journal of the National Comprehensive Cancer Network (2022)
Comments on Surgeon-Patient Sex Concordance and Postoperative Outcomes
Authors: Yuan-Ya Liao, James Cheng-Chung Wei, Hsin-Yi Shu
Journal: JAMA Surgery (2022)

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Correction: Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee
Authors: James L. Januzzi, Joseph M. Garasic, Scott E. Kasner, Vickie McDonald, Mark C. Petrie, Jonathan Seltzer, Michael Mauro, Kevin Croce, Ellin Berman, Michael Deininger, Andreas Hochhaus, Javier Pinilla-Ibarz, Franck Nicolini, Dong-Wook Kim, Daniel J. DeAngelo, Hagop Kantarjian, Jing Xu, Tracey Hall, Shouryadeep Srivastava, Daniel Naranjo, Jorge Cortes
Journal: Journal of Hematology & Oncology (2022)
APABETALONE DOWNREGULATES PATHWAYS ASSOCIATED WITH NEPHROPATHY IN RENAL MESANGIAL CELLS WHICH MAY CONTRIBUTE TO REDUCED CARDIAC EVENTS OBSERVED IN CKD PATIENTS
Authors: Dean Gilham, Li Fu, Brooke D. Rakai, Laura Tsujikawa, Sylwia Wasiak, Stephanie Stotz, Christopher D. Sarsons, Norman C. Wong, Michael Sweeney, Jan O. Johansson, Kamyar KalantarZadeh, Ewelina Kulikowski
Journal: Journal of the American College of Cardiology (2022)
Repurposing Vandetanib plus Everolimus for the Treatment of<i>ACVR1</i>-Mutant Diffuse Intrinsic Pontine Glioma
Authors: Diana M. Carvalho, Peter J. Richardson, Nagore Olaciregui, Reda Stankunaite, Cinzia Lavarino, Valeria Molinari, Elizabeth A. Corley, Daniel P. Smith, Ruth Ruddle, Adam Donovan, Akos Pal, Florence I. Raynaud, Sara Temelso, Alan Mackay, John P. Overington, Anne Phelan, David Sheppard, Andrew Mackinnon, Bassel Zebian, Safa Al-Sarraj, Ashirwad Merve, Jeremy Pryce, Jacques Grill, Michael Hubank, Ofelia Cruz, Andres Morales La Madrid, Sabine Mueller, Angel M. Carcaboso, Fernando Carceller, Chris Jones
Journal: Cancer Discovery (2021)

Somatic mutations in ACVR1 are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to search for approved compounds for ACVR1-mutant DIPG, the combination of vandetanib and everolimus was identified as a possible therapeutic approach. Vandetanib, an inhibitor of VEGFR/RET/EGFR, was found to target ACVR1 (K d = 150 nmol/L) and reduce DIPG cell viability in vitro but has limited ability to cross the blood-brain barrier. In addition to mTOR, everolimus inhibited ABCG2 (BCRP) and ABCB1 (P-gp) transporters and was synergistic in DIPG cells when combined with vandetanib in vitro. This combination was well tolerated in vivo and significantly extended survival and reduced tumor burden in an orthotopic ACVR1-mutant patient-derived DIPG xenograft model. Four patients with ACVR1-mutant DIPG were treated with vandetanib plus an mTOR inhibitor, informing the dosing and toxicity profile of this combination for future clinical studies. SIGNIFICANCE: Twenty-five percent of patients with the incurable brainstem tumor DIPG harbor somatic activating mutations in ACVR1, but there are no approved drugs targeting the receptor. Using artificial intelligence, we identify and validate, both experimentally and clinically, the novel combination of vandetanib and everolimus in these children based on both signaling and pharmacokinetic synergies.This article is highlighted in the In This Issue feature, p. 275.
LONG TERM OUTCOMES OF CONGENITALLY CORRECTED TRANSPOSITION OF THE GREAT ARTERIES WITH BIVENTRICULAR PHYSIOLOGY
Authors: Razleen Brar, Aisha Zia, Miza Salim Hammoud, Samantha Xu, Jeevanantham Rajeswaran, Tara Karamlou, Rukmini Komarlu
Journal: Journal of the American College of Cardiology (2022)
An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice
Authors: Etsuro Nanishi, Francesco Borriello, Timothy R. O’Meara, Marisa E. McGrath, Yoshine Saito, Robert E. Haupt, Hyuk-Soo Seo, Simon D. van Haren, Cecilia B. Cavazzoni, Byron Brook, Soumik Barman, Jing Chen, Joann Diray-Arce, Simon Doss-Gollin, Maria De Leon, Alejandra Prevost-Reilly, Katherine Chew, Manisha Menon, Kijun Song, Andrew Z. Xu, Timothy M. Caradonna, Jared Feldman, Blake M. Hauser, Aaron G. Schmidt, Amy C. Sherman, Lindsey R. Baden, Robert K. Ernst, Carly Dillen, Stuart M. Weston, Robert M. Johnson, Holly L. Hammond, Romana Mayer, Allen Burke, Maria E. Bottazzi, Peter J. Hotez, Ulrich Strych, Aiquan Chang, Jingyou Yu, Peter T. Sage, Dan H. Barouch, Sirano Dhe-Paganon, Ivan Zanoni, Al Ozonoff, Matthew B. Frieman, Ofer Levy, David J. Dowling
Journal: Science Translational Medicine (2022)

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need. The receptor binding domain (RBD) is a key target of SARS-CoV-2 neutralizing antibodies but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists alone or formulated with aluminum hydroxide (AH) and benchmarked them against AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that an AH and CpG adjuvant formulation (AH:CpG) produced an 80-fold increase in anti-RBD neutralizing antibody titers in both age groups relative to AH alone and protected aged mice from the SARS-CoV-2 challenge. The AH:CpG-adjuvanted RBD vaccine elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.
Outcomes After SARS-CoV-2 Vaccination Among Children With a History of Multisystem Inflammatory Syndrome
Authors: Matthew Wisniewski, Angela Chun, Stefano Volpi, Eyal Muscal, S. Kristen Sexson Tejtel, Flor Munoz, Tiphanie P. Vogel
Journal: JAMA Network Open (2022)

Nitai Levy, MD; Jordanna H. Koppel, MD; Or Kaplan, MD; Hadas Yechiam, MD; Keren Shahar-Nissan, MD; Naama Kuchinski Cohen, MD; Itai Shavit, MD
Risk factors associated with acute respiratory illnesses in athletes: a systematic review by a subgroup of the IOC consensus on ‘acute respiratory illness in the athlete’
Authors: Wayne Derman, Marelise Badenhorst, Maaike Eken, Josu Gomez-Ezeiza, Jane Fitzpatrick, Maree Gleeson, Lovemore Kunorozva, Katja Mjosund, Margo Mountjoy, Nicola Sewry, Martin Schwellnus
Journal: British Journal of Sports Medicine (2022)

Objective To review risk factors associated with acute respiratory illness (ARill) in athletes, including non-infectious ARill and suspected or confirmed acute respiratory infections (ARinf). Design Systematic review. Data sources Electronic databases: PubMed-Medline, EbscoHost and Web of Science. Eligibility criteria Original research articles published between January 1990 and July 2020 in English were searched for prospective and retrospective full text studies that reported quantitative data on risk factors associated with ARill/ARinf in athletes, at any level of performance (elite/non-elite), aged 15–65 years. Results 48 studies (n=19 390 athletes) were included in the study. Risk factors associated with ARill/ARinf were: increased training monotony, endurance training programmes, lack of tapering, training during winter or at altitude, international travel and vitamin D deficits. Low tear-(SIgA) and salivary-(IgA) were immune biomarkers associated with ARill/ARinf. Conclusions Modifiable training and environmental risk factors could be considered by sports coaches and athletes to reduce the risk of ARill/ARinf. Clinicians working with athletes can consider assessing and treating specific nutritional deficiencies such as vitamin D. More research regarding the role and clinical application of measuring immune biomarkers in athletes at high risk of ARill/ARinf is warranted. PROSPERO registration number CRD42020160928.
Low-cost gastrointestinal manometry via silicone–liquid-metal pressure transducers resembling a quipu
Authors: Kewang Nan, Sahab Babaee, Walter W. Chan, Johannes L. P. Kuosmanen, Vivian R. Feig, Yiyue Luo, Shriya S. Srinivasan, Christina M. Patterson, Ahmad Mujtaba Jebran, Giovanni Traverso
Journal: Nature Biomedical Engineering (2022)
LONG-TERM MAJOR ADVERSE CARDIOVASCULAR OUTCOMES IN PATIENTS WITH MYOCARDIAL INJURY AND TYPE 1 AND 2 MYOCARDIAL INFARCTION
Authors: Jonathan Knott, Olatunde Oladipupo Ola, Laura De Michieli, Ashok Akula, Ramila Mehta, Marshall Dworak, Erika Crockford, Ronstan Lobo, Nicholas Rastas, Swetha Karturi, Scott Wohlrab, David O. Hodge, Eric Grube, Tahir Tak, Charles R. Cagin, Rajiv Gulati, Allan S. Jaffe, Yader Sandoval
Journal: Journal of the American College of Cardiology (2022)
Author Correction: Benchmarking transposable element annotation methods for creation of a streamlined, comprehensive pipeline
Authors: Shujun Ou, Weijia Su, Yi Liao, Kapeel Chougule, Jireh R. A. Agda, Adam J. Hellinga, Carlos Santiago Blanco Lugo, Tyler A. Elliott, Doreen Ware, Thomas Peterson, Ning Jiang, Candice N. Hirsch, Matthew B. Hufford
Journal: Genome biology (2022)
Abstract P5-10-07: A preclinical evaluation of the isoform-specific PI3K inhibitor in HER2+ breast cancer models with resistance to trastuzumab
Authors: Pradip De, Jennifer Carlson Aske, Nandini Dey
Journal: Cancer Research (2022)

Abstract Background: The PI3K pathway mediates trastuzumab resistance. However, early attempts to indirectly target this signaling pathway with everolimus had limited success. We hypothesize that isoform-specific PI3K inhibitors may enhance the efficacy of anti-HER2 therapy. Methods: We conducted a preclinical proof-of-concept in vitro study of the selective PI3K alpha/delta inhibitor copanlisib or PI3K alpha inhibitor alpelisib alone and in combination with either trastuzumab (hmAB) or tucatinib (HER2-specific kinase inhibitor) in HER2 amplified breast cancer cell lines including trastuzumab-resistant (BT474HR), PIK3CA mutated/HER2 amplified (HCC1954 &amp; MDA-MB453) and PIK3CA wild type/HER2 amplified (SKBR3). Results: When used alone or in combination with the HER2 targeted therapies trastuzumab or tucatinib, copanlisib and alpelisib have anti-proliferative effects in real-time cell proliferation or 3D-ON-TOP assays. Both isoform-specific inhibitors dose-dependently inhibited PI3K signaling and were effective regardless of trastuzumab-resistant and PIK3CA status. Compared to alpelisib, copanlisib was more effective in inducing apoptosis by Annexin V staining. Tucantinib dose-dependently blocked HER2 phosphorylation and p-HER2-SHC-GRB2-mediated MAPK signaling. Significantly, the combination of HER2-targeted therapy (trastuzumab or tucatinib) and copanlisib/alpelisib more effectively inhibited both 3D-ON-TOP colony formation and the HER2 downstream signaling cascade than either drug alone. Conclusion: Our study shows that blocking the PI3K pathway is an essential determinant of response to anti-HER2 regimens in trastuzumab-resistant breast cancers. Citation Format: Pradip De, Jennifer Carlson Aske, Nandini Dey. A preclinical evaluation of the isoform-specific PI3K inhibitor in HER2+ breast cancer models with resistance to trastuzumab [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-10-07.
The emerging role of bile acids as critical components in nanotechnology and bioengineering: Pharmacology, formulation optimizers and hydrogel-biomaterial applications
Authors: Bozica Kovacevic, Melissa Jones, Corina Ionescu, Daniel Walker, Susbin Wagle, Jacqueline Chester, Thomas Foster, Daniel Brown, Momir Mikov, Armin Mooranian, Hani Al-Salami
Journal: Biomaterials (2022)
DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics
Authors: Lingfang Zhuang, Kangni Jia, Chen Chen, Zhigang Li, Jiaxin Zhao, Jian Hu, Hang Zhang, Qin Fan, Chunkai Huang, Hongyang Xie, Lin Lu, Weifeng Shen, Guang Ning, Jiqiu Wang, Ruiyan Zhang, Kang Chen, Xiaoxiang Yan
Journal: Circulation (2022)

Background: Heart failure is a global public health issue that is associated with increasing morbidity and mortality. Previous studies have suggested that mitochondrial dysfunction plays critical roles in the progression of heart failure; however, the underlying mechanisms remain unclear. Because kinases have been reported to modulate mitochondrial function, we investigated the effects of DYRK1B (dual-specificity tyrosine-regulated kinase 1B) on mitochondrial bioenergetics, cardiac hypertrophy, and heart failure. Methods: We engineered DYRK1B transgenic and knockout mice and used transverse aortic constriction to produce an in vivo model of cardiac hypertrophy. The effects of DYRK1B and its downstream mediators were subsequently elucidated using RNA-sequencing analysis and mitochondrial functional analysis. Results: We found that DYRK1B expression was clearly upregulated in failing human myocardium and in hypertrophic murine hearts, as well. Cardiac-specific DYRK1B overexpression resulted in cardiac dysfunction accompanied by a decline in the left ventricular ejection fraction, fraction shortening, and increased cardiac fibrosis. In striking contrast to DYRK1B overexpression, the deletion of DYRK1B mitigated transverse aortic constriction–induced cardiac hypertrophy and heart failure. Mechanistically, DYRK1B was positively associated with impaired mitochondrial bioenergetics by directly binding with STAT3 to increase its phosphorylation and nuclear accumulation, ultimately contributing toward the downregulation of PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α). Furthermore, the inhibition of DYRK1B or STAT3 activity using specific inhibitors was able to restore cardiac performance by rejuvenating mitochondrial bioenergetics. Conclusions: Taken together, the findings of this study provide new insights into the previously unrecognized role of DYRK1B in mitochondrial bioenergetics and the progression of cardiac hypertrophy and heart failure. Consequently, these findings may provide new therapeutic options for patients with heart failure.
Modulation of tissue resident memory T cells by glucocorticoids after acute cellular rejection in lung transplantation
Authors: Mark E. Snyder, Kaveh Moghbeli, Anna Bondonese, Andrew Craig, Iulia Popescu, Li Fan, Tracy Tabib, Robert Lafyatis, Kong Chen, Humberto E. Trejo Bittar, Elizabeth Lendermon, Joseph Pilewski, Bruce Johnson, Silpa Kilaru, Yingze Zhang, Pablo G. Sanchez, Jonathan K. Alder, Peter A. Sims, John F. McDyer
Journal: The Journal of Experimental Medicine (2022)

Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single-cell RNA and TCR sequencing on recipient-derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with rejection and compare them with T cells obtained from the same patients after treatment of rejection with high-dose systemic glucocorticoids. At the time of rejection, we found an oligoclonal expansion of cytotoxic CD8+ T cells that all persisted as tissue resident memory T cells after successful treatment. Persisting CD8+ allograft-resident T cells have reduced gene expression for cytotoxic mediators after therapy with glucocorticoids but accumulate around airways. This clonal expansion is discordant with circulating T cell clonal expansion at the time of rejection, suggesting in situ expansion. We thus highlight the accumulation of cytotoxic, recipient-derived tissue resident memory T cells within the lung allograft that persist despite the administration of high-dose systemic glucocorticoids. The long-term clinical consequences of this persistence have yet to be characterized.
Ethnic differences in success at application for consultant posts among United Kingdom physicians from 2011 to 2019: a retrospective cross-sectional observational study
Authors: PR Harvey, C Phillips, N Newbery, D Nagamoottoo, K Woolf, NJ Trudgill
Journal: Journal of the Royal Society of Medicine (2022)

Summary Objectives To identify associations between success following application for consultant physician posts and demographic factors. Design Logistic regression analysis of nationwide survey data. Setting United Kingdom (UK) physicians with a recent certificate of completion of training (CCT). Participants All UK trainee physicians who received a CCT between 2010 and 2019 were surveyed. Respondents were excluded if they had not applied for a consultant post or if application data were incomplete. Main outcome measures The primary outcome measure was success over the entire consultant application process, i.e. shortlisted and offered the post following the first application. Secondary outcomes were: shortlisted following first application and offered a consultant post at first interview. Results From 7037 CCT holders surveyed, 50.7% responded. While 1198 (59.7%) respondents were white, 760 (37.9%) were from minority ethnic groups and 50 (3.5%) were of unknown ethnicity. Primary medical qualification (PMQ) country was the UK in 75.3% (n = 1512). On multivariable logistic regression analysis the independent negative associations with success were: minority ethnicity (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.43–0.71); p &lt; 0.001) vs. white; PMQ from Europe (OR 0.47, 95% CI 0.28–0.79; p = 0.004) or Asia (OR 0.68, 95% CI 0.49–0.96; p = 0.027) vs. UK PMQ; year of CCT 2012 (OR 0.40, 95% CI 0.24–0.68; p = 0.001), 2013 (OR 0.39, 95% CI 0.23–0.65; p &lt; 0.001), and 2014 (OR 0.26, 95% CI 0.15–0.43; p &lt; 0.001) vs. 2019. Specialties associated with lower success rates included Cardiology, Endocrinology, Genitourinary medicine, Palliative care, Renal and Respiratory, compared to Acute medicine. Conclusions Minority ethnic group candidates for consultant physician posts had lower success rates compared to white candidates after correction for important variables including specialty, time from and country of PMQ. This finding requires further evaluation to identify the causes for this variation.