tbuckley/cabot-search huggingface dataset:
COVID-19 Vaccination Effectiveness Against Infection or Death in a National U.S. Health Care System
Authors: George N. Ioannou, Emily R. Locke, Ann M. O’Hare, Amy S.B. Bohnert, Edward J. Boyko, Denise M. Hynes, Kristin Berry
Journal: Annals of Internal Medicine (2021)

Little is known about real-world COVID-19 vaccine effectiveness (VE) in racially and ethnically diverse, elderly populations with high comorbidity burden.To determine the effectiveness of messenger RNA COVID-19 vaccines.Target trial emulation study comparing newly vaccinated persons with matched unvaccinated controls.U.S. Department of Veterans Affairs health care system.Among persons receiving care in the Veterans Affairs health care system (n = 5 766 638), those who received at least 1 dose of the Moderna or Pfizer-BioNTech COVID-19 vaccine from 11 December 2020 to 25 March 2021 (n = 2 099 871) were matched to unvaccinated controls in a 1:1 ratio according to demographic, clinical, and geographic characteristics.Follow-up for SARS-CoV-2 infection or SARS-CoV-2-related death, defined as death within 30 days of infection, began after the vaccination date or an identical index date for the matched unvaccinated controls and continued until up to 30 June 2021.Vaccine effectiveness against SARS-CoV-2 infection or SARS-CoV-2-related death.Vaccinated and unvaccinated groups were well matched; both were predominantly male (92.9% vs. 93.4%), had advanced age (mean, 68.7 years in both groups), had diverse racial and ethnic distribution (for example, Black: 17.3% vs. 17.0%, Hispanic: 6.5% vs. 6.1%), and had substantial comorbidity burden. Vaccine effectiveness 7 or more days after the second vaccine dose was 69% (95% CI, 67% to 70%) against SARS-CoV-2 infection and 86% (CI, 82% to 89%) against SARS-CoV-2-related death and was similar when follow-up was extended to 31 March versus 30 June. Vaccine effectiveness against infection decreased with increasing age and comorbidity burden.Predominantly male population and lack of data on SARS-CoV-2 variants.In an elderly, diverse, high-comorbidity population, COVID-19 VE against infection was substantially lower than previously reported, but VE against death was high. Complementary infection mitigation efforts remain important for pandemic control, even with vaccination.U.S. Department of Veterans Affairs.
Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial
Authors: Nathan Hale Fowler, Michael Dickinson, Martin Dreyling, Joaquin Martinez-Lopez, Arne Kolstad, Jason Butler, Monalisa Ghosh, Leslie Popplewell, Julio C. Chavez, Emmanuel Bachy, Koji Kato, Hideo Harigae, Marie José Kersten, Charalambos Andreadis, Peter A. Riedell, P. Joy Ho, José Antonio Pérez-Simón, Andy I. Chen, Loretta J. Nastoupil, Bastian von Tresckow, Andrés José María Ferreri, Takanori Teshima, Piers E. M. Patten, Joseph P. McGuirk, Andreas L. Petzer, Fritz Offner, Andreas Viardot, Pier Luigi Zinzani, Ram Malladi, Aiesha Zia, Rakesh Awasthi, Aisha Masood, Oezlem Anak, Stephen J. Schuster, Catherine Thieblemont
Journal: Nature Medicine (2021)
Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A
Authors: Wayne L. Furman, Beth McCarville, Barry L. Shulkin, Andrew Davidoff, Matthew Krasin, Chia-Wei Hsu, Haitao Pan, Jianrong Wu, Rachel Brennan, Michael W. Bishop, Sara Helmig, Elizabeth Stewart, Fariba Navid, Brandon Triplett, Victor Santana, Teresa Santiago, Jacquelyn A. Hank, Stephen D. Gillies, Alice Yu, Paul M. Sondel, Wing H. Leung, Alberto Pappo, Sara M. Federico
Journal: Journal of Clinical Oncology (2021)

We evaluated whether combining a humanized antidisialoganglioside monoclonal antibody (hu14.18K322A) throughout therapy improves early response and outcomes in children with newly diagnosed high-risk neuroblastoma.
Neuropathology and molecular diagnosis of Synucleinopathies
Authors: Shunsuke Koga, Hiroaki Sekiya, Naveen Kondru, Owen A. Ross, Dennis W. Dickson
Journal: Molecular Neurodegeneration (2021)

Synucleinopathies are clinically and pathologically heterogeneous disorders characterized by pathologic aggregates of α-synuclein in neurons and glia, in the form of Lewy bodies, Lewy neurites, neuronal cytoplasmic inclusions, and glial cytoplasmic inclusions. Synucleinopathies can be divided into two major disease entities: Lewy body disease and multiple system atrophy (MSA). Common clinical presentations of Lewy body disease are Parkinson's disease (PD), PD with dementia, and dementia with Lewy bodies (DLB), while MSA has two major clinical subtypes, MSA with predominant cerebellar ataxia and MSA with predominant parkinsonism. There are currently no disease-modifying therapies for the synucleinopathies, but information obtained from molecular genetics and models that explore mechanisms of α-synuclein conversion to pathologic oligomers and insoluble fibrils offer hope for eventual therapies. It remains unclear how α-synuclein can be associated with distinct cellular pathologies (e.g., Lewy bodies and glial cytoplasmic inclusions) and what factors determine neuroanatomical and cell type vulnerability. Accumulating evidence from in vitro and in vivo experiments suggests that α-synuclein species derived from Lewy body disease and MSA are distinct "strains" having different seeding properties. Recent advancements in in vitro seeding assays, such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), not only demonstrate distinct seeding activity in the synucleinopathies, but also offer exciting opportunities for molecular diagnosis using readily accessible peripheral tissue samples. Cryogenic electron microscopy (cryo-EM) structural studies of α-synuclein derived from recombinant or brain-derived filaments provide new insight into mechanisms of seeding in synucleinopathies. In this review, we describe clinical, genetic and neuropathologic features of synucleinopathies, including a discussion of the evolution of classification and staging of Lewy body disease. We also provide a brief discussion on proposed mechanisms of Lewy body formation, as well as evidence supporting the existence of distinct α-synuclein strains in Lewy body disease and MSA.
Unifying mechanism behind the onset of acquired epilepsy
Authors: Yuri Zilberter, Irina Popova, Misha Zilberter
Journal: Trends in Pharmacological Sciences (2021)

Acquired epilepsy (AE) can result from a number of brain insults and neurological diseases with wide etiological diversity sharing one common outcome of brain epileptiform activity. This implies that despite their disparity, all these initiating pathologies affect the same fundamental brain functions underlying network excitability. Identifying such mechanisms and their availability as therapeutic targets would help develop an effective strategy for epileptogenesis prevention. In this opinion article, we propose that the vicious cycle of NADPH oxidase (NOX)-mediated oxidative stress and glucose hypometabolism is the underlying cause of AE, as available data reveal a critical role for both pathologies in epileptogenesis and the process of seizure initiation. Altogether, here we present a novel view on the mechanisms behind the onset of AE and identify therapeutic targets for potential clinical applications.
Health Care Utilization Among Texas Veterans Health Administration Enrollees Before and After Hurricane Harvey, 2016-2018
Authors: Margaret Carrel, Gosia S. Clore, Seungwon Kim, Mary Vaughan Sarrazin, Eric Tate, Eli N. Perencevich, Michihiko Goto
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Hurricanes and flooding can interrupt health care utilization. Understanding the magnitude and duration of interruptions, as well as how they vary according to hazard exposure, race, and income, are important for identifying populations in need of greater retention in care. <h3>Objective</h3> To determine how the differential exposure to Hurricane Harvey in August 2017 is associated with changes in utilization of Veterans Health Administration health care. <h3>Design, Setting, and Participants</h3> This is a retrospective cohort analysis of primary care practitioner (PCP) visits, emergency department visits, and inpatient admissions in the Veterans Health Administration among Texas veterans residing in counties impacted by Hurricane Harvey from 2016 to 2018. Data analysis was performed from September 2020 to May 2021. <h3>Exposures</h3> Residential flooding after Hurricane Harvey. <h3>Main Outcomes and Measures</h3> Interrupted time series analysis measured changes in health care utilization over time, stratified by residential flood exposure, race, and income. <h3>Results</h3> Of the 99 858 patients in the cohort, 89 931 (90.06%) were male, and their median (range) age was 58 (21 to 102) years. Compared with veterans in nonflooded areas, veterans living in flooded areas were more likely to be Black (24 715 veterans [33.80%] vs 4237 veterans [15.85%]) and low-income (14 895 veterans [20.37%] vs 4853 veterans [18.15%]). Rates of PCP visits decreased by 49.78% (95% CI, −64.52% to −35.15%) for veterans in flooded areas and by 45.89% (95% CI, −61.93% to −29.91%) for veterans in nonflooded areas and did not rebound until more than 8 weeks after the hurricane. Rates of PCP visits in flooded areas remained lower than expected for 11 weeks among White veterans (−6.99%; 95% CI, −14.36% to 0.81%) and for 13 weeks among racial minority veterans (−7.22%; 95% CI, −14.11% to 0.30%). Low-income veterans, regardless of flood status, experienced greater suppression of PCP visits in the 8 weeks following the hurricane (−13.72%; 95% CI, −20.51% to −6.68%) compared with their wealthier counterparts (−9.63%; 95% CI, −16.74% to −2.26%). <h3>Conclusions and Relevance</h3> These findings suggest that flood disasters such as Hurricane Harvey may be associated with declines in health care utilization that differ according to flood status, race, and income strata. Patients most exposed to the disaster also had the greatest delay or nonreceipt of care.
Abstract 8894: Post-Resuscitation Diastolic Blood Pressure is a Better Predictive Factor for Outcomes of Cardiac Arrest Patients
Authors: ChienYu Chi, Herman Chih-Heng Chang, Min-Shan Tsai, CHIEN-HUA HUANG
Journal: Circulation (2021)

Introduction: Post-resuscitation hemodynamic level was associated with outcomes. Our study hypothesized that post-resuscitation diastolic blood pressure (DBP) was a better predictive factor for outcomes. Methods: Starting from TaIwan Network of Targeted Temperature ManagEment for CARDiac Arrest (TIMECARD) registry, we recruited 540 adult patients who received target temperature management (TTM) during January 2014 and September 2019. After excluding 37 patients with pre-arrest cerebral performance categories scale (CPC) 3-4 and 55 patients with extracorporeal membrane oxygenation support, 448 patients were analyzed. Patient’s characteristics, comorbidities, resuscitation factors, arrest etiologies, systolic blood pressure (SBP) and DBP after resuscitation were included for analysis. Primary outcomes were survival of discharge (SOD) and discharge with favorable neurologic outcomes (CPC 1-2). Univariate and multivariate analysis were performed to identify favorable predictors. Predictive values of SBP and DBP for both outcomes were compared by calculating area under receiver operating characteristic (AUC). Results: Among 448 patients, 182 (40.7%) patients had SOD and 89 (19.9%) patients had CPC 1-2. DBP was significantly higher in patients with SOD (p&lt;0.001) and CPC 1-2 (p=0.003). In multivariate analysis, DBP was also an independent factor for SOD (p=0.004) and CPC 1-2 (p =0.048). When comparing SBP and DBP, DBP was a better predictor for CPC 1-2 (SBP AUC: 0.58 vs DBP AUC: 0.64, p=0.003). In subgroup analysis, DBP &gt; 80 served as a favorable predictor for both SOD and CPC 1-2. When comparing patients with DBP &lt;80 and SBP &gt;80, patients with higher DBP values had significantly higher percentage of cardiac etiologies arrest and relative higher percentage of initial shockable rhythm. Conclusion: DBP is a better hemodynamic parameter than SBP for predicting outcomes. In multivariate model, DBP &gt; 80 was an independent predictor for better survival and favorable neurologic outcomes.
77P The Belgian Multidisciplinary Immunotoxicity Board (BITOX): A nationwide initiative of the Belgian Society of Medical Oncology (BSMO)
Authors: M. Verhaert, S. Aspeslagh, O. Bechter, S. Wuyts, N. Blockx, M. Brandao, J. Dekervel, B. Neyns, A. Rutten, E. Seront, E. Wauters, M.S. Schreuer, A. Drowart
Journal: Annals of Oncology (2021)
High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Authors: Jennifer S. Chen, Ryan D. Chow, Eric Song, Tianyang Mao, Benjamin Israelow, Kathy Kamath, Joel Bozekowski, Winston A. Haynes, Renata B. Filler, Bridget L. Menasche, Jin Wei, Mia Madel Alfajaro, Wenzhi Song, Lei Peng, Lauren Carter, Jason S. Weinstein, Uthaman Gowthaman, Sidi Chen, Joe Craft, John C. Shon, Akiko Iwasaki, Craig B. Wilen, Stephanie C. Eisenbarth
Journal: Science Immunology (2022)

T follicular helper (T
Robust immune responses are observed after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2–experienced individuals
Authors: Marie I. Samanovic, Amber R. Cornelius, Sophie L. Gray-Gaillard, Joseph Richard Allen, Trishala Karmacharya, Jimmy P. Wilson, Sara Wesley Hyman, Michael Tuen, Sergei B. Koralov, Mark J. Mulligan, Ramin Sedaghat Herati
Journal: Science Translational Medicine (2022)

The use of coronavirus disease 2019 (COVID-19) vaccines will play the major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccines have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with a prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccines differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 15 adults who had experienced COVID-19, compared to 21 adults who did not have prior COVID-19. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8 + T cell responses in both cohorts after the second dose. Furthermore, SARS-CoV-2–naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses after each dose of vaccine, whereas SARS-CoV-2–experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but these responses were not further enhanced after the second dose of the vaccine at the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have implications for personalizing mRNA vaccination regimens used to prevent COVID-19, including for the deployment of booster shots.
A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates
Authors: M. Gordon Joyce, Hannah A. D. King, Ines Elakhal-Naouar, Aslaa Ahmed, Kristina K. Peachman, Camila Macedo Cincotta, Caroline Subra, Rita E. Chen, Paul V. Thomas, Wei-Hung Chen, Rajeshwer S. Sankhala, Agnes Hajduczki, Elizabeth J. Martinez, Caroline E. Peterson, William C. Chang, Misook Choe, Clayton Smith, Parker J. Lee, Jarrett A. Headley, Mekdi G. Taddese, Hanne A. Elyard, Anthony Cook, Alexander Anderson, Kathryn McGuckin Wuertz, Ming Dong, Isabella Swafford, James Brett Case, Jeffrey R. Currier, Kerri G. Lal, Sebastian Molnar, Manoj S. Nair, Vincent Dussupt, Sharon P. Daye, Xiankun Zeng, Erica K. Barkei, Hilary M. Staples, Kendra Alfson, Ricardo Carrion, Shelly J. Krebs, Dominic Paquin-Proulx, Nicos Karasavva, Victoria R. Polonis, Linda L. Jagodzinski, Mihret F. Amare, Sandhya Vasan, Paul T. Scott, Yaoxing Huang, David D. Ho, Natalia de Val, Michael S. Diamond, Mark G. Lewis, Mangala Rao, Gary R. Matyas, Gregory D. Gromowski, Sheila A. Peel, Nelson L. Michael, Diane L. Bolton, Kayvon Modjarrad
Journal: Science Translational Medicine (2022)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (T H 1)–biased CD4 T H response and elicited neutralizing antibodies against SARS-CoV-2 wild type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates after high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates support the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.
Phase I study of tipifarnib and sorafenib in patients with biopsiable advanced cancers (NCI protocol 7156 supported by NCI grant UO1 CA062461)
Authors: D. S. Hong, L. Camacho, C. Ng, J. Wright, R. A. Newman, S. Moulder, N. Tannir, J. Wheler, R. Khan, R. Kurzrock
Journal: Journal of Clinical Oncology (2007)

3549 Background: The Ras and Raf kinases are sequential signaling proteins in the MAPK pathway and inhibition of both targets may confer synergistic effects, particularly in tumors with activation of either kinase through mutation or other mechanisms. Therefore, we sought to combine sorafenib, a multikinase inhibitor (Raf, VEGFR, PDGFR) and tipifarnib an inhibitor of farnesyltransferase that is critical for Ras activity in a phase I study to determine the safety, pharmacokinetics (PK), and tumor response. Methods: The trial was a phase I trial of advanced cancer patients(pts) with a conventional dose escalation design. Each cycle consisted of 28 days of sorafenib and 21 days of tipifarnib. Dose levels are listed in the table . Results: To date, a total of 27 pts have been enrolled (median age 54.5 yrs, M:F 1:1. 3 RCC, 3 breast, 4 sarcoma, 4 melanoma, 3 CRC, 4 thyroid, 2 H&amp;N, one thymic, one adrenal cortical, one SCC of the lung, and one unknown primary SCC). Two pts developed grade 3 DLT-skin rash on the first dosing level (tipifarnib at 100 mg po BID and sorafenib at 400 mg po BID). Dose escalation was modified as per table below. At dose level 4, 2/5 pts entered experienced a DLT of grade 3 rash and grade 3 drug fever, therefore MTD has been determined to be tipifarnib 100 mg BID, sorafenib 400 mg qam, 200 mg qpm. The most common treatment related toxicities included lymphopenia (18), hyperglycemia (17), and skin rash (14). Currently, 19 of the 27 pts are evaluable; 13 pts had SD (8–44 weeks); 2 RCC pts for 32 weeks, an adrenal cortical ca pt for 32 weeks, one melanoma pt for 44 weeks. PK analysis suggested findings similar to single agent PK profiles, no PK interactions were apparent. Conclusions: Significant toxicity with the combination of these two agents, even doses well below single agent maximum levels were observed. The MTD was determined to be tipifarnib at 100 mg BID, sorafenib at 400 mg qam, 200 mg qpm. PK analysis, to date show,no pharmacokinetic interaction between tipifarnib and sorafenib. [Table: see text] [Table: see text]
Soundings: Medical thaumaturgy
Authors: George Dunea
Journal: BMJ (2003)

It is by no means easy to perform miracles on this earth, in this age of scepticism and of evidence based incredulity.

But things are different at 35 000 feet, in an airplane, high up above the clouds. Here a qualified miracle worker may notice the red spots of Dr Henry Koplik of New York (1858-1927) and relieve the anxiety verging on hysteria of the mother of a blotchy, sniffly, febrile, loud, brattish child. He will “cure” the “stroke suspect” with a transient ulnar palsy sustained from sitting too long in economy class. He will wake up the heavy-set businessman who briefly passed out after drinking too much whisky in first class. With impeccable skill he will manage a confusing arrhythmia by applying an electrode to the chest of a man with an impalpable pulse. He will open the miracle box and press the green button, obey the injunction not to defibrillate, and witness with relief a spontaneous return to sinus rhythm.

But on the ground Italy is the best country for miracles. Imagine, for example, the crowded train from Ferrara to Bologna: a call for dottore; anxious relatives gathered around a cyanosed woman foaming at the mouth. No stethoscope, rudimentary Italian only. Doctor holds up jaw, makes her sit up, then waits. Woman deeply unconscious, not sweating, niente diabetes, no response to painful stimuli, pinpoint pupils. Could it be a pontine haemorrhage? But lifting one leg to test plantar reflexes has miraculous effect. Behold, she moves. Pupils dilate.

In a few minutes she stands up. Mumbles. Gropes around for her handbag. In Bologna a mustachioed conductor and a comely policewoman take over; time to take one's leave and run to catch last train for Milan.

On the outskirts of the baroque town of Lecce, under the hot Apulian sun, a young nun in full habit is seen bending over an older woman on the sidewalk. Blood everywhere. Mother down from Rome to visit daughter nun; wears sandals only; steps on a piece of glass. Dramatic intervention: tiny puncture wound on sole of foot; nun's handkerchief applied for 20 minutes; bleeding stops. Then it is time to move on, to other tasks, just as San Giorgio di Lecce might have done in the days when dragons infested the countryside, elfins danced on many a green mead, and miracle men walked about the land.
Abstract 14132: The Association of Volume of Patients Admitted with ST Elevation Myocardial Infarction, and the Proportion receiving Primary Percutaneous Coronary Intervention, with Time Delays and Mortality: The Myocardial Ischaemia National Audit Project (MINAP) 2004-7.
Authors: Christopher P Gale, Robert M West, Brian A Cattle, Iain Squire, Mark A De Belder, Keith A Fox, Alistair S Hall, Ian R Pearson, Roger Boyle, James M McLenachan, Phillip D Batin, Darren C Greenwood
Journal: Circulation (2010)

Aims: To study determinants of door-to-balloon (DTB) times for the primary PCI (pPCI) service for ST-elevation myocardial infarction (STEMI) in England and Wales between 2004 and 2007. Methods and ...