tbuckley/cabot-search huggingface dataset:
COVID-19 and blood type in Atlanta
Authors: V. Sueblinvong, M. J. Kaalla, A. Mehta, Emory, Covid-Quality, Clinical
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Introduction: The purpose of this study was to determine if there are any associations with severity of illness from Coronavirus disease 2019 (COVID-19) and ABO blood group among a cohort of critically ill patients admitted to the intensive care unit across the Emory Healthcare System. Since COVID-19 was first identified, many research groups across the country have worked to identify potential risk factors for the development of severe disease. Specifically, there have been some reports of a possible association between blood type A and a higher risk of infection and mortality, while other groups have determined that no such association exists. We sought to determine if ABO blood group was associated with higher rates of intubation, mortality, or inflammatory markers at our institution. Methods: We analyzed data from the electronic medical record (EMR) of all patients who were admitted to the hospital with COVID-19 at any of the Emory Hospitals between March 6, 2020 and May 5, 2020. The data were collected by the Emory COVID-19 Quality and Clinical Research Collaborative, and we included and analyzed data from patients who had data available for blood group and spent any time in the intensive care unit during their hospitalization. We used the Chi-square test to determine if death or intubation were associated with blood group and ANOVA when comparing inflammatory markers between the blood groups. Results: A total of 192 patients in the cohort had data available for blood type and among them 47 patients had blood group A (24.5%) vs 42% nationally, 48 had blood group B (25.0%) vs 10%, 9 had blood group AB (4.7%) vs 4%, and 88 had blood group O (45.8%) vs 44%. Death and intubation were not associated with any blood group type (p=0.424 and p=0.144, respectively). Values for inflammatory markers (CRP, IL-6, D-dimer, WBC, and ferritin) were not significantly different between the different blood groups (p=0.654, p=0.357, p=0.060, p=0.083, and p=0.706, respectively). Conclusions: When compared to data from the American Red Cross, blood group B was more prevalent in our cohort compared to the general population of the US. There was no association between blood group type and death or mechanical ventilation. We noted a trend towards higher D-dimer levels and WBC counts in patients with blood group B, but overall, there were no significant differences between inflammatory markers and blood group types among critically ill patients with COVID-19.
Oncolytic parainfluenza virus combines with NK cells to mediate killing of infected and non-infected lung cancer cells within 3D spheroids: role of type I and type III interferon signaling
Authors: Namita Varudkar, Jeremiah L Oyer, Alicja Copik, Griffith D Parks
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background There is intense interest in developing novel oncolytic viruses, which can be used in cancer therapies along with immune cells such as natural killer (NK) cells. We have previously developed a particle-based method for in vitro expansion of highly cytotoxic human NK cells (PM21-NK cells). Here, we have tested the hypothesis that oncolytic parainfluenza virus 5 (P/V virus) can combine with PM21-NK cells for targeted killing of lung cancer cells. Methods PM21-NK cells were assayed for killing of P/V virus-infected A549, H1299 and Calu-1 lung cancer cells in two-dimensional (2D) and three-dimensional (3D) cultures using flow cytometry, luminescence and kinetic imaging-based methods. Blocking antibodies were used to evaluate NK cell activating receptors involved in PM21-NK cell killing of infected target cells. Media transfer experiments tested soluble factors that increase PM21-NK cell killing of both P/V virus-infected and uninfected tumor cells. Results In 2D cultures, PM21-NK cells efficiently killed P/V virus-infected cancer cells compared with non-infected cells, through involvement of the viral glycoprotein and NK cell receptors NKp30, NKp46 and NKG2D. In 3D spheroid cultures, P/V virus infection was restricted to the outer layer of the spheroid. However, PM21-NK cells were able to more efficiently kill both the outer layer of infected cells in the spheroid and progressing further to kill the uninfected interior cells. Media transfer experiments demonstrated that P/V virus infection produced both type I and type III interferons, which decreased cell growth, which contributed to a reduction in the overall number of uninfected tumor cells in conjunction with PM21-NK cells. Across five cancer cell lines, the contribution of P/V virus infection on PM21-NK cell killing of target cells correlated with interferon induction. Conclusion Our data support the potential of combining oncolytic parainfluenza virus with PM21-NK cell adoptive therapy against lung cancer.
Providing Family-Centered Intensive Care Unit Care Without Family Presence—Human Connection in the Time of COVID-19
Authors: Deepshikha Charan Ashana, Christopher E. Cox
Journal: JAMA Network Open (2021)

Nancy Kentish-Barnes, PhD; Zoé Cohen-Solal, MS; Lucas Morin, PhD; Virginie Souppart, RN; Frédéric Pochard, MD, PhD; Elie Azoulay, MD, PhD
Abstract 200: Role of Silent Mating Type Information Regulation 2 Homolog - 6 in Wound Healing in Diabetes
Authors: Rajarajan Amirthalingam Thandavarayan, Darukeshwara Joladarashi, Prince Jeyabal, Sahana Suresh Babu, Suresh K Verma, Garikipati Venkata Naga Srikanth, Mohsin Khan, Raj Kishore, Prasanna Krishnamurthy
Journal: Circulation Research (2016)

Delayed wound healing is one of the major complications in diabetes and is characterized by chronic proinflammatory response, and abnormalities in angiogenesis and collagen deposition. Sirtuin family proteins regulate numerous pathophysiological processes, including those involved in promotion of longevity, DNA repair, glycolysis and inflammation. However, the role of sirtuin 6 (SIRT6), a NAD+-dependent nuclear deacetylase, in wound healing specifically under diabetic condition remains unclear. To analyse the role of SIRT6 in cutaneous wound healing, paired 6-mm stented wound was created in diabetic db/db mice and injected siRNA against SIRT6 in the wound margins (transfection agent alone and nonsense siRNA served as controls). Wound time to closure was assessed by digital planimetry, and wounds were harvested for histology, immunohistochemistry and Western blotting. SIRT6-siRNA-treated diabetic wound showed impaired healing, which was associated with reduced capillary density (CD31-staining vessels) when compared to control treatment. Interestingly, SIRT6 deficiency decreased vascular endothelial growth factor expression and proliferation markers in the wounds. Furthermore, SIRT6 ablation in diabetic wound promotes nuclear factor-κB (NF-κB) activation resulting in increased expression of proinflammatory markers (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-α and interleukin-1β) and increased oxidative stress. Collectively, our findings demonstrate that loss of SIRT6 in cutaneous wound aggravates proinflammatory response by increasing NF-κB activation, oxidative stress and decrease in angiogenesis in the diabetic mice. Based on these findings, we speculate that the activation of SIRT6 signalling might be a potential therapeutic approach for promoting wound healing in diabetics.
The Combination of GROβ and AMD3100 Leads to Rapid and Robust Mobilization of Hematopoietic Stem Cells in Nonhuman Primates
Authors: Patrick C. Falahee, Kevin A. Goncalves, Sharon L. Hyzy, Jennifer L. Proctor, Jonathan Hoggatt, Dwight Morrow, Michael P. Cooke
Journal: Blood (2017)
CD8 <sup>+</sup> T cells specific for conserved coronavirus epitopes correlate with milder disease in patients with COVID-19
Authors: Vamsee Mallajosyula, Conner Ganjavi, Saborni Chakraborty, Alana M. McSween, Ana Jimena Pavlovitch-Bedzyk, Julie Wilhelmy, Allison Nau, Monali Manohar, Kari C. Nadeau, Mark M. Davis
Journal: Science Immunology (2021)

A central feature of the SARS-CoV-2 pandemic is that some individuals become severely ill or die, whereas others have only a mild disease course or are asymptomatic. Here we report development of an improved multimeric αβ T cell staining reagent platform, with each maxi-ferritin "spheromer" displaying 12 peptide-MHC complexes. Spheromers stain specific T cells more efficiently than peptide-MHC tetramers and capture a broader portion of the sequence repertoire for a given peptide-MHC. Analyzing the response in unexposed individuals, we find that T cells recognizing peptides conserved amongst coronaviruses are more abundant and tend to have a "memory" phenotype, compared to those unique to SARS-CoV-2. Significantly, CD8
Governments and public trust: a public covid inquiry that reported quickly could shape response to the third wave
Authors: John Puntis, Tony O’Sullivan
Journal: BMJ (2021)

Godlee says that it takes both time and hard work to regain lost trust.1 The prime minister has committed to preparing for a public inquiry into the pandemic next year, promising it will be fully independent and have “the ability to compel the production of all relevant materials and take oral evidence in public, under oath.”2

The People’s Covid Inquiry,34 under the chairmanship of Michael Mansfield QC, has just finished hearing testimony …
Targeted smoking cessation for dual users of combustible and electronic cigarettes: a randomised controlled trial
Authors: Ursula Martinez, Vani N Simmons, Steven K Sutton, David J Drobes, Lauren R Meltzer, Karen O Brandon, Margaret M Byrne, Paul T Harrell, Thomas Eissenberg, Christopher R Bullen, Thomas H Brandon
Journal: The Lancet Public Health (2021)

Although many smokers use electronic cigarettes (e-cigarettes) to quit smoking, most continue to smoke while vaping. This dual use might delay cessation and increase toxicant exposure. We aimed to test the efficacy of a self-help intervention designed to help dual users to quit smoking.In this three-arm randomised controlled trial we recruited individuals in the USA using Facebook and multimedia advertisements. Included participants were 18 years or older, smoked at least weekly in the preceding year, and vaped at least weekly in the preceding month. We used computer generated randomisation with balanced-permuted blocks (block size 10, with 2-4-4 ratio) to allocate participants to assessment only (ASSESS group), generic smoking cessation self-help booklets (GENERIC group), or booklets targeting dual users (eTARGET group). Individuals in the generic or targeted intervention groups received monthly cessation materials for 18 months, with assessments every 3 months for 24 months. The main outcome was self-reported 7-day point-prevalence smoking abstinence at each assessment point. All randomly allocated participants were included in primary analyses using generalised estimating equations for each of 20 datasets created by multiple imputation. Analysis of the χ2s produced an F test. The trial is registered with ClinicalTrials.gov, NCT02416011, and is now closed.Between July 12, 2016, and June 30, 2017, we randomly assigned 2896 dual users (575 to assessment, 1154 to generic intervention, and 1167 to targeted self-help). 7-day point-prevalence smoking abstinence increased from 14% at 3 months to 42% at 24 months (F7,541·7=67·1, p<0·0001) in the overall sample. Targeted self-help resulted in higher smoking abstinence than did assessment alone throughout the treatment period (F1,973·8=10·20, p=0·0014 [α=0·017]). The generic intervention group had abstinence rates between those of the assessment and targeted groups, but did not significantly differ from either when adjusted for multiple comparisons (GENERIC vs eTARGET F1,1102·5=1·79, p=0·18 [α=0·05]; GENERIC vs ASSESS F1,676·7=4·29, p=0·039 [α=0·025]). Differences between study groups attenuated after the interventions ended.A targeted self-help intervention with high potential for dissemination could be efficacious in promoting smoking cessation among dual users of combustible cigarettes and e-cigarettes.National Institute on Drug Abuse, National Cancer Institute.
Covid-19: Third vaccine dose boosts immune response but may not be needed, say researchers
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The interval between the first and second doses of the Oxford AstraZeneca vaccine can be extended up to 10 months and a third dose of the vaccine provides a strong boost to the immune response, according to preliminary results.

In a preprint, published on 28 June,1 researchers from the University of Oxford reported that extending the interval between the first and second dose to 45 weeks resulted in higher antibody titres. They also found that a third dose given 44 to 45 weeks after the second increased antibody titres further, and that adverse events were lower after the second or third dose than after the first.

Researchers said the results are positive, especially for areas affected by vaccine shortages, as they could provide “greater flexibility in vaccination schedules.” But they said that currently there is no …
Long COVID in a prospective cohort of home-isolated patients
Authors: Bjørn Blomberg, Kristin Greve-Isdahl Mohn, Karl Albert Brokstad, Fan Zhou, Dagrun Waag Linchausen, Bent-Are Hansen, Sarah Lartey, Therese Bredholt Onyango, Kanika Kuwelker, Marianne Sævik, Hauke Bartsch, Camilla Tøndel, Bård Reiakvam Kittang, Anders Madsen, Geir Bredholt, Juha Vahokoski, Elisabeth Berg Fjelltveit, Amit Bansal, Mai Chi Trieu, Sonja Ljostveit, Jan Stefan Olofsson, Nina Ertesvåg, Helene Heitmann Sandnes, Anette Corydon, Hanne Søyland, Marianne Eidsheim, Kjerstin Jakobsen, Nina Guldseth, Synnøve Hauge, Rebecca Jane Cox, Nina Langeland
Journal: Nature Medicine (2021)

Abstract Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients—247 home-isolated and 65 hospitalized—comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16–30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.
Quantitative Microbial Risk Assessment for Contaminated Private Wells in the Fractured Dolomite Aquifer of Kewaunee County, Wisconsin
Authors: Tucker R. Burch, Joel P. Stokdyk, Susan K. Spencer, Burney A. Kieke, Aaron D. Firnstahl, Maureen A. Muldoon, Mark A. Borchardt
Journal: Environmental Health Perspectives (2021)

Private wells are an important source of drinking water in Kewaunee County, Wisconsin. Due to the region's fractured dolomite aquifer, these wells are vulnerable to contamination by human and zoonotic gastrointestinal pathogens originating from land-applied cattle manure and private septic systems.
Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II-III Trial
Authors: Shukui Qin, Feng Bi, Shanzhi Gu, Yuxian Bai, Zhendong Chen, Zishu Wang, Jieer Ying, Yinying Lu, Zhiqiang Meng, Hongming Pan, Ping Yang, Helong Zhang, Xi Chen, Aibing Xu, Chengxu Cui, Bo Zhu, Jian Wu, Xiaoli Xin, Jufeng Wang, Jinlu Shan, Junhui Chen, Zhendong Zheng, Li Xu, Xiaoyu Wen, Zhenyu You, Zhenggang Ren, Xiufeng Liu, Meng Qiu, Liqing Wu, Feng Chen
Journal: Journal of Clinical Oncology (2021)

Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC.This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients.Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months (P = .0570). The objective response rate was 4.6% v 2.7% (P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] v 165 [50%]; P = .0018).Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.
Respiratory disease, and treatment / thematic poster session COVID-19 as a cause of pulmonary fibrosis
Authors: B. Heyman, J. Solomon, J. Ko, D. A. Lynch, S. Raia, R. Condos
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Long term sequelae of COVID-19, especially pertaining to lung structure and function, are largely unknown. Patients with severe COVID-19 who develop acute respiratory distress syndrome (ARDS) requiring prolonged mechanical ventilation are likely at highest risk. We sought to determine the incidence of radiographic markers of lung fibrosis and associated risk factors in a cohort of patients with severe COVID-19. Methods: The Electronic Medical Record at New York University was queried for subjects without a history of interstitial lung disease who had a positive SARS-CoV-2 PCR, required mechanical ventilation, and had a chest computed tomography (CT) conducted during their hospitalization for COVID-19. Clinical and laboratory data was collected. CT scans were blindly read by a thoracic radiologist using a novel scoring system where fibrotic changes were defined as consolidation and/or ground glass with traction, and honeycombing. The prevalence of fibrosis was established and analyses were done to evaluate for clinical associations. Data is represented as number of patients (percent of cohort), and mean ± standard deviation). Results: 88 patients were included, 61 (69.3%) had fibrotic changes on CT done 50.3 ± 33.6 days after admission, while 27 (30.7%) had no fibrosis seen on CT done 41.5 ± 26.0 days after admission. There were no significant differences in demographics or medical history between the subgroups. The fibrotic subgroup required mechanical ventilation for a longer duration than the non-fibrotic subgroup (52.8 ± 33.2 vs 32.1 ± 18.8 days) and had higher plateau pressures 21 days after intubation (26.6 ± 6.0 vs 16.5 ± 5.4 cmH2O). P/F ratios were similar on day of intubation (145.4 ± 55.5 fibrotic vs 145.7 ± 64.1 non-fibrotic), however the fibrotic subgroup had lower P/F ratios 7 days after intubation (146.3 ± 57.0 vs 182.1 ± 63.3), 14 days after intubation (166.3 ± 83.7 vs 236.8 ± 84.3), and 21 days after intubation (170.8 ± 90.5 vs 249.5 ± 103.0). The fibrotic subgroup also had higher peak ferritin (8899.92 ± 11461.3 vs 6715.6 ± 9680.1 ng/mL) and LDH (1031.67 ± 628.9 vs 929.0 ± 493.3 U/L). Conclusion: In our cohort of severe COVID-19 patients, over two-thirds had fibrotic changes on CT chest. Longer duration of mechanical ventilation, higher plateau pressures 21 days after intubation, lower P/F ratios 7 days or more after intubation, and higher peak ferritin and LDH levels were associated with presence of fibrosis. .
Inhibition of Unc-51 like Autophagy Activating Kinase 1 (ULK1) Is Highly Synergistic with Chemotherapy and Bcl2 Inhibition in Acute Myeloid Leukemia (AML)
Authors: Seemana Bhattacharya, Sujan Piya, Teresa McQueen, Marina Konopleva, Michael Andreeff, Gautam Borthakur
Journal: Blood (2017)
New Insights into F-Cells, F-Reticulocytes and the Role of Fetal Hemoglobin in Protecting Sickle Red Cells from Hemolysis upon Mechanical Stress
Authors: Sara El Hoss, Maria Alejandra Lizarralde Iragorri, Valentine Brousse, Michaël Dussiot, Sophie Lefevre, Alexander Rodrigo Ferreira, Yann Lamarre, Ana Cristina Silva Pinto, Simone Kashima, Claudine Lapoumeroulie, Dimas Tadeu Covas, Caroline Le Van Kim, Yves Colin Aronovicz, Jacques Elion, Olivier Français, Bruno Le Pioufle, Wassim El Nemer
Journal: Blood (2017)
Six figure compensation is expected for family of patient who died from starvation at Surrey hospital
Authors: Clare Dyer
Journal: BMJ (2021)

The family of a patient who starved to death in hospital are expected to receive a six figure sum in an out-of-court settlement with the trust that cared for her in the last months of her life.

Surrey assistant coroner Anna Crawford found that Linda Doherty, 69, died from sepsis and acute kidney injury, malnutrition, intestinal failure secondary to Crohn’s disease and ileal resection, and inadequate nutritional intake.

Towards the end of her three month stay in East Surrey Hospital in 2017 the team looking after her failed to recognise that she had malnutrition, weight loss, and intestinal failure. The coroner found that she was inadequately nourished from 23 June until the time of her death on 7 August. But had she been given total parenteral nutrition from 11 July onwards she would have survived, the coroner …
再分極特性評価のための187-チャンネル信号平均ベクトル投影ECG(187ch SAVP-ECG)の信頼性:体表面87-leadECGによる比較研究
Authors: Matsuyama Yuko, Nirei Takashi, Nakai Kenji, Kasanuki Hiroshi
Journal: Circulation (2008)
Dissecting the Fitness Costs of Complex Mutations
Authors: Pablo Yubero, Juan F Poyatos
Journal: Molecular Biology and Evolution (2021)

Abstract The fitness cost of complex pleiotropic mutations is generally difficult to assess. On the one hand, it is necessary to identify which molecular properties are directly altered by the mutation. On the other, this alteration modifies the activity of many genetic targets with uncertain consequences. Here, we examine the possibility of addressing these challenges by identifying unique predictors of these costs. To this aim, we consider mutations in the RNA polymerase (RNAP) in Escherichia coli as a model of complex mutations. Changes in RNAP modify the global program of transcriptional regulation, with many consequences. Among others is the difficulty to decouple the direct effect of the mutation from the response of the whole system to such mutation. A problem that we solve quantitatively with data of a set of constitutive genes, those on which the global program acts most directly. We provide a statistical framework that incorporates the direct effects and other molecular variables linked to this program as predictors, which leads to the identification that some genes are more suitable to determine costs than others. Therefore, we not only identified which molecular properties best anticipate fitness, but we also present the paradoxical result that, despite pleiotropy, specific genes serve as more solid predictors. These results have connotations for the understanding of the architecture of robustness in biological systems.