tbuckley/cabot-search huggingface dataset:
Balanced Crystalloids versus Saline in Critically Ill Adults with Hyperkalemia or Acute Kidney Injury: Secondary Analysis of a Clinical Trial
Authors: Alexandra H. Toporek, Matthew W. Semler, Wesley H. Self, Gordon R. Bernard, Li Wang, Edward D. Siew, Joanna L. Stollings, Jonathan P. Wanderer, Todd W. Rice, Jonathan D. Casey
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Definition of abbreviations: AKI 5 acute kidney injury; CKD 5 chronic kidney disease (stage 3 or greater); N/A 5 not applicable; RRT 5 renal replacement therapy.Continuous data are presented as median (25th percentile-75th percentile) unless otherwise noted.*Chronic kidney disease stage 3 or greater is defined as a glomerular filtration rate of ,60 ml/min per 1.73 m 2 as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation using the patient's baseline creatinine concentration.† Patients who had received RRT before admission were excluded from the cohort of patients with AKI on admission.‡ Patients who had received RRT before ICU admission were excluded from calculations of AKI and creatinine at baseline and were ineligible to meet the clinical outcome criteria for new RRT or new AKI developing after enrollment.§ Stage 2 or greater AKI is defined using the Kidney Disease Improving Global Outcomes creatinine criteria (7) as any creatinine value between ICU admission and discharge or 30 days that is 1) increased at least 0.3 mg/dl from a preceding post-ICU admission value and 2) at least 200% of the baseline value, at least 200% of a preceding post-ICU admission value, or at least 4.0 mg/dl; or new receipt of RRT.jj The University Health Consortium index is a severity-of-illness score calculated using variables available on hospital admission to provide an estimation of mortality from 0% to 100%.¶ Cumulative volume of fluid ordered from ICU admission through Day 30 includes fluid ordered both in the ICU and after transfer out of the ICU.Balanced crystalloid includes lactated Ringer's and Plasma-Lyte A. **Data on potassium-lowering therapies only available among patients with hyperkalemia on ICU admission.
SAT0163 Risk factors related to low heel bone mineral density in postmenopausal women
Authors: JA Román-Ivorra, L Abad, C Fernández-Carballido, JJ Alegre-Sancho, B Pérez, A Pérez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To analyse the relationship between risk factors of osteoporosis (OP) and heel bone mineral density (BMD) in postmenopausal women in a Mediterranean area. <h3>Methods</h3> 170 postmenopausal women were consecutively selected for an osteoporosis screening. In all women we collected the following data: age, BMI (body mass index), years since menopause, pregnancy, breed-feeding, maternal hip fracture; use of coffee, alcohol and tobacco; daily calcium intake, sun exposure and previous fractures (distal forearm, vertebral, hip and other non-traumatic fractures). A measurement of heel BMD was done in all women with PIXI bone densitometer (Lunar). Dorso-lumbar x-rays were reviewed in all patients. Chi-square, Student or Fisher tests were used for the statistical analysis. <h3>Results</h3> Significative differences between patients with normal values of BMD and OP were detected only for the following risk factors: <h3>Conclusion</h3> Previous fractures, mother’s hip fracture, low BMI, age and years since menopause are factors associated with low heel BMD. So, PIXI is a good method for OP screening in postmenopausal women.
Phase I study of the novel pro-drug MIV-818 in patients with hepatocellular carcinoma, intra-hepatic cholangiocarcinoma or liver metastases.
Authors: T.R. Jeffry Evans, Eric Van Cutsem, Hans Prenen, Mark R. Middleton, Debashis Sarker, Karin Tunblad, Fredrik Oberg, Tom Morris, Linda Basse, Elizabeth Ruth Plummer
Journal: Journal of Clinical Oncology (2021)

309 Background: MIV-818 is an orally administered troxacitabine (TRX)-based nucleotide prodrug. It is highly metabolized by human hepatocytes, directing high levels of the chain-terminating nucleotide tri-phosphate to the liver, while minimizing exposure to other organs. The tri-phosphate is incorporated into DNA during replication, which leads to DNA double strand breaks, DNA damage responses, and cytotoxicity. Methods: Patients (pts), ≥18 years, ECOG performance status &lt; 1, adequate organ function, with treatment-refractory hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA) or liver metastases (LM) from solid tumors were enrolled. In phase Ia, MIV-818 monotherapy was administered in an intra-patient dose-escalation design with doses of 3-70mg for 3-5 days in cycles of 21 days. Phase Ib is an inter-patient dose escalation in a 3+3 cohort design and is currently ongoing. Treatment is given until disease progression or unacceptable toxicity. The primary objective is to assess safety and tolerability and, for phase Ia, also to establish the starting dose for phase Ib. Key secondary objective was to evaluate the overall response rate based on RECIST v1.1. The pharmacokinetics of MIV-818 and its metabolites were evaluated, and on-treatment liver biopsies were collected to assess the pharmacokinetics and the pharmacodynamic effects of MIV-818. Results: Nine patients (7M; 2F), ECOG performance status 0 (n=3) or 1 (n=6), median age = 57 years (range: 50-84) with HCC (2 pts), iCCA (1) or LM (6) from solid tumors (mainly GI tract), previously treated with median 2 (1-5) lines of therapy, were included in phase Ia. Patients were dosed up to 60 mg 5 days/week. The most common treatment related AEs were those in the hematological system: neutropenia grade (gr) 1-4, neutropenic sepsis gr 4; thrombocytopenia gr 1-2, anemia gr 1-2. Elevated bilirubin gr 1-3 and liver enzymes gr 3 were also reported. Most of the AEs were reversible. Five pts discontinued due to AE and 4 pts discontinued due to progressive disease outside the liver after 2-4 cycles. Starting dose of phase Ib was determined to be 40mg 5 days/week. Tumor biopsies showed evidence of selective DNA damage in tumor tissue, including in hypoxic regions, with minimal or no impact of MIV-818 observed in healthy liver tissue. Conclusions: MIV-818 had an acceptable safety and tolerability profile. Biomarker data of liver biopsies demonstrated a selective effect of MIV-818 on cancer cells. Updated safety and efficacy data from phase Ib will be presented at the meeting. (NCT03781934). Clinical trial information: 2018-000995-14.
Covid-19: Doctors in Norway told to assess severely frail patients for vaccination
Authors: Ingrid Torjesen
Journal: BMJ (2021)

Covid-19: Doctors in Norway told to assess severely frail patients for vaccination Ingrid Torjesen Doctors in Norway have been advised to assess severely frail and terminally ill patients to determine whether the benefits of vaccination outweigh the risks of possible side effects, after reports indicated that vaccine side effects may have led to deterioration and death of some patients.
Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion
Authors: Eduardo Salinas, Maude Boisvert, Amit A. Upadhyay, Nathalie Bédard, Sydney A. Nelson, Julie Bruneau, Cynthia A. Derdeyn, Joseph Marcotrigiano, Matthew J. Evans, Steven E. Bosinger, Naglaa H. Shoukry, Arash Grakoui
Journal: Journal of Clinical Investigation (2021)

Early appearance of neutralizing antibodies during acute hepatitis C virus (HCV) infection is associated with spontaneous viral clearance. However, the longitudinal changes in antigen-specific memory B cell (MBCs) associated with divergent HCV infection outcomes remain undefined. We characterized longitudinal changes in E2 glycoprotein-specific MBCs from subjects who either spontaneously resolved acute HCV infection or progressed to chronic infection, using single-cell RNA-seq and functional assays. HCV-specific antibodies in plasma from chronically infected subjects recognized multiple E2 genotypes, while those from spontaneous resolvers exhibited variable cross-reactivity to heterotypic E2. E2-specific MBCs from spontaneous resolvers peaked early after infection (4-6 months), following expansion of activated circulating T follicular helper cells (cTfh) expressing interleukin 21. In contrast, E2-specific MBCs from chronically infected subjects, enriched in VH1-69, expanded during persistent infection (> 1 year), in the absence of significantly activated cTfh expansion. Early E2-specific MBCs from spontaneous resolvers produced monoclonal antibodies (mAbs) with fewer somatic hypermutations and lower E2 binding but similar neutralization as mAbs from late E2-specific MBCs of chronically infected subjects. These findings indicate that early cTfh activity accelerates expansion of E2-specific MBCs during acute infection, which might contribute to spontaneous clearance of HCV.
Abstract 14512: Blood Reservoir Function in Fontan Patients With Asplenia Syndrome
Authors: Shun Matsumura, Akiko Yana, Seiko Kuwata, Clara Kurishima, Hirofumi Saiki, Yoichi Iwamoto, Kenji Sugamoto, Hirotaka Ishido, Satoshi Masutani, Hideaki Senzaki
Journal: Circulation (2018)

Background: The splanchnic circulation constitutes a major portion of the total vasculature capacitance and plays an important role in maintaining blood perfusion to vital organs in cases of hemody...
Exploring trans people’s experiences of adoption and fostering in the United Kingdom: A qualitative study
Authors: Claire Brown
Journal: International Journal of Transgender Health (2021)

Trans people's voices have routinely been silenced or subsumed within research on adoption or fostering by lesbian, gay and bisexual people. The lack of inclusion of trans people within adoption and fostering research and practice not only disadvantages trans carers, but also children needing foster and adoptive homes. The present paper addresses the need to bring the experiences of trans carers to the forefront of adoption and fostering research.The study sought to explore the experiences of trans people in relation to adoption and fostering in the United Kingdom.A narrative inquiry was conducted using in-depth, semi-structured interviews and inductive thematic analysis to examine the subjective experiences of individuals who are trans or non-binary. Participants were recruited via purposive and snowballing sampling methods; using fliers sent via email to community groups and centres, social media and research network advertisement. People were eligible to take part if they were resident in the United Kingdom, over twenty-one years, and had adopted/fostered or applied/planned to apply to adopt or foster. Eight participants were included in this research, representing a variety of genders and ages.The thematic analysis resulted in the development of five themes: 1) Motivation to adopt or foster, 2) Perceived institutional barriers to pursuing adoption or fostering, 3) Experiences of cisgenderism in assessment, 4) Experiences of cisgenderism at placement, and 5) Positive experiences and recommendations.The findings highlighted the impact that cisgenderism can have in the context of adoption and fostering, whereby multiple barriers exist that impact trans and non-binary people interested in adoption and fostering. It is suggested that effective training should be implemented to increase understanding of gender diversity and address gender barriers in adoption and fostering social work.
Prolongation of minimal action potential duration in sustained fibrillation decreases complexity by transient destabilization
Authors: P. E. Wolkowicz, P. K. Umeda, O. F. Sharifov, P. Wang, H. Mahtani, F. Urthaler
Journal: Cardiovascular Research (2013)

We read with great interest the article by Bingen et al .1 entitled ‘Prolongation of minimal action potential duration in sustained fibrillation decreases complexity by transient destabilization’. This paper referred to our report that 2-aminoethoxydiphenyl borate (2APB) induces fibrillation in perfused rat hearts2 (http://youtu.be/pDsm0UKQvt4, http://youtu.be/J0q_YPZyBwk). It also extended our work3–7 and that of Huo et al .8 by establishing the arrhythmicity of 2APB in monolayers of neonatal rat ventricular myocytes. Bingen proposed that 2APB provokes electrical instability by inhibiting cardiac connexins which leads to impulse re-entry. They also concluded that prolonging the action potential with Bay K 8644 or barium reduces ectopic complexity to a few re-entrant sources. We would like to highlight four points that are inconsistent with these analyses and suggest an alternate, possibly complementary, explanation for 2APB arrhythmicity.7

First, the concentrations of 2APB that initiate sporadic ectopy (∼10 µM)1,3 do not affect connexin 43 and 45.9 Furthermore, 15–20 µM …
Cancer-related distress among multiplemyeloma patients during the COVID-19 pandemic
Authors: N. W. Sweeney, J. Ahlstrom
Journal: Clinical Cancer Research (2020)

Background: The rapid outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to thedelay of non-urgent or routine medical appointments, placing tremendous burden on cancer patients  Meanwhile, the emotional effect of the novel coronavirus (COVID-19) on high-risk groups, such as multiple myeloma (MM)patients, remains unclear  The purpose of this project was to understand psychosocial distress and unmet needsamong patients with active MM during the acute phase of social distancing and COVID-19 impact in the UnitedStates  Methods: We utilized HealthTree (healthtree org) and invited patients with active MM cancer or precursor conditionsto participate in an online survey curated through a partnership with the Cancer Support Community (CSC) Participants were asked to rate their level of concern (Not at All to Very Seriously) on 12 items assessingpsychosocial, practical, and physical needs (selected from CSC's CancerSupportSource® distress screening tool)during the COVID-19 pandemic  De-identified responses were aggregated and reviewed  The survey wasdetermined to be exempt by the Western Institutional Review Board  Results: 1,079 MM pts participated in the survey between April 15, 2020 and June 8, 2020  The percentages ofpatients responding moderately to very seriously concerned are reported here  Eating and nutrition (71%), sleepproblems (49%), pain and/or physical discomfort (46%), and feeling too tired to do the things you need or want to do(44%) made up the physical/health concerns  Psychosocial/emotional concerns included worrying about the futureand what lies ahead (46%), worry about family, children, and/or friends (44%), feeling irritable (37%), feeling sad ordepressed (30%), feeling nervous or afraid (25%), feeling lonely or isolated (20%), and relationship problems withyour spouse/partner (11%)  Finally, 32% reported insurance or money concerns  Conclusions: Respondents to our survey were most concerned with eating and nutrition, sleep problems, painand/or physical discomfort, and worrying about the future  Informing patients and medical professionals of physicaland psychosocial distress experienced by patients could create a unified approach to decreasing distress levels andincrease patient overall health, even during a pandemic or when care is delayed  Patient-reported surveys via anonline portal, like HealthTree, can help investigators assess the patient community and result in hypothesis-generating research questions to enhance patient outcomes
Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung cancer
Authors: Shaocong Wu, Min Luo, Kenneth K. W. To, Jianye Zhang, Chaoyue Su, Hong Zhang, Sainan An, Fang Wang, Da Chen, Liwu Fu
Journal: Molecular Cancer (2021)

Abstract Background Epidermal growth factor receptor (EGFR)-mutated lung cancer constitutes a major subgroup of non-small cell lung cancer (NSCLC) and osimertinib is administrated as first-line treatment. However, most patients with osimertinib treatment eventually relapse within one year. The underlying mechanisms of osimertinib resistance remain largely unexplored. Methods Exosomes isolation was performed by differential centrifugation. Co-culture assays were conducted to explore the alteration of drug sensitivity by cell viability and apoptosis assays. Immunofluorescence and flow cytometry were performed to visualize the formation or absorption of exosomes. Exosomes secretion was measured by Nanoparticle Tracking Analysis or ELISA. The xenograft tumor model in mice was established to evaluate the effect of exosomes on osimertinib sensitivity in vivo. Results Intercellular transfer of exosomal wild type EGFR protein confers osimertinib resistance to EGFR-mutated sensitive cancer cells in vitro and in vivo. Co-culture of EGFR-mutated sensitive cells and EGFR-nonmutated resistant cells promoted osimertinib resistance phenotype in EGFR-mutated cancer cells, while depletion of exosomes from conditioned medium or blockade of exosomal EGFR by neutralizing antibody alleviated this phenotype. Mechanistically, osimertinib promoted the release of exosomes by upregulated a Rab GTPase (RAB17). Knockdown of RAB17 resulted in the decrease of exosomes secretion. Moreover, exosomes could be internalized by EGFR-mutated cancer cells via Clathrin-dependent endocytosis and then the encapsulated exosomal wild type EGFR protein activated downstream PI3K/AKT and MAPK signaling pathways and triggered osimertinib resistance. Conclusions Intercellular transfer of exosomal wild type EGFR promotes osimertinib resistance in NSCLC, which may represent a novel resistant mechanism of osimertinib and provide a proof of concept for targeting exosomes to prevent and reverse the osimertinib resistance.
Adapter Chimeric Antigen Receptor (aCAR)-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Universal Tumor Targeting
Authors: Stefan Grote, Christian M. Seitz, Simon Diepold, Markus Buchner, Caroline Baden, Elke Malenke, Sophie Marie Dieckmann, Hanna Schwaemmle, Joerg Mittelstaet, Andrew Kaiser, Patrick Schlegel, Rupert Handgretinger, Sabine Schleicher
Journal: Blood (2018)
FRI0068 LIPID PROFILE AND BONE MINERAL DENSITY IN PATIENTS WITH RHEUMATOID ARTHRITIS: IS THERE AN ADDED RISK OF OSTEOPOROSIS?
Authors: B. Touil, H. Azzouzi, O. Lamkhanat, F. Chennouf, I. Linda
Journal: Annals of the Rheumatic Diseases (2020)

Background: Bone is a target in many inflammatory rheumatic diseases such as rheumatoid arthritis (RA). It has been supposed that an atherogenic lipid profile could be associated with lower bone mineral density (BMD) and vertebral fractures (VF). Objectives: We aimed to evaluate the relationship between the lipid profile, BMD and the presence of VF in RA patients. Methods: A cross sectional study was conducted in a population of 169 established RA. In each subject we evaluated the body mass index (BMI), tobacco use, alcohol consumption, presence of diabetes and high blood pression, lipid profile (total cholesterol (TC), High density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), triglycerides (TG), and VF. RA characteristics were also assessed (disease duration, disease activity score (DAS), auto antibodies, corticosteroid intake, and secondary sjogren’s syndrome). BMD was measured by dual energy X-ray absorptiometry (DXA) in lumbar spine and femoral neck. Logistic and linear regression were performed with SPSS 20, both BMD and VF were assessed as dependent variables. Results: The mean age was 55.5±11.9 years, with a female predominance (152 women). The average BMI was 26.79 ± 5.36. We had 24.3 % of hypertensive patients and 16.6 % of diabetics. The average lipid concentrations were 4.39±1 mmol/L for TC, 1.293±0.36 mmol/L for HDLc, 2.74±0.80 mmol/L for LDLc and 1.25±0.62 mmol/L for TG. At the linear regression there was no correlation between plasma lipid concentrations and BMD, whether at the lumbar spine or the femoral neck. However we found a significant correlation between VF and high TC concentrations (p=0.043, OR: 2.864, 95% IC [1.036-7.922]). At the multivariate regression, high TC levels were still associated with VF, adjusted in BMI, age and the duration of corticosteroid use (p=0.006, OR: 6.07, 95% CI[1.69- 21.77]). The same finding was observed between high concentrations of HDLc and the prevalence of VF adjusted in the same variables (p=0.006, OR: 197.01, 95% CI [4.64-8363.51]). Conclusion: Although there was no relation between lipid plasma levels and BMD in our population. There was a significant association between high concentrations of TC, HDLc and the prevalence of VF. Disclosure of Interests: None declared
Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease
Authors: Reisa Sperling, David Henley, Paul S. Aisen, Rema Raman, Michael C. Donohue, Karin Ernstrom, Michael S. Rafii, Johannes Streffer, Yingqi Shi, Keith Karcher, Nandini Raghavan, Yevgen Tymofyeyev, Jennifer Bogert, H. Robert Brashear, Gerald Novak, John Thipphawong, Ziad S. Saad, Hartmuth Kolb, Hany Rofael, Panna Sanga, Gary Romano
Journal: JAMA Neurology (2021)

Atabecestat, a nonselective oral β-secretase inhibitor, was evaluated in the EARLY trial for slowing cognitive decline in participants with preclinical Alzheimer disease. Preliminary analyses suggested dose-related cognitive worsening and neuropsychiatric adverse events (AEs).To report efficacy, safety, and biomarker findings in the EARLY trial, both on and off atabecestat treatment, with focus on potential recovery of effects on cognition and behavior.Randomized, double-blind, placebo-controlled, phase 2b/3 study conducted from November 2015 to December 2018 after being stopped prematurely. The study was conducted at 143 centers across 14 countries. Participants were permitted to be followed off-treatment by the original protocol, collecting safety and efficacy data. From 4464 screened participants, 557 amyloid-positive, cognitively normal (Clinical Dementia Rating of 0; aged 60-85 years) participants (approximately 34% of originally planned 1650) were randomized before the trial sponsor stopped enrollment.Participants were randomized (1:1:1) to atabecestat, 5 mg (n = 189), 25 mg (n = 183), or placebo (n = 185).Primary outcome: change from baseline in Preclinical Alzheimer Cognitive Composite score. Secondary outcomes: change from baseline in the Cognitive Function Index and the Repeatable Battery for the Assessment of Neuropsychological Status total scale score. Safety was monitored throughout the study.Of 557 participants, 341 were women (61.2%); mean (SD) age was 70.4 (5.56) years. In May 2018, study medication was stopped early owing to hepatic-related AEs; participants were followed up off-treatment for 6 months. Atabecestat, 25 mg, showed significant cognitive worsening vs placebo for Preclinical Alzheimer Cognitive Composite at month 6 (least-square mean difference, -1.09; 95% CI, -1.66 to -0.53; P < .001) and month 12 (least-square mean, -1.62; 95% CI, -2.49 to -0.76; P < .001), and at month 3 for Repeatable Battery for the Assessment of Neuropsychological Status (least-square mean, -3.70; 95% CI, -5.76 to -1.63; P < .001). Cognitive Function Index participant report showed nonsignificant worsening at month 12. Systemic and neuropsychiatric-related treatment-emergent AEs were greater in atabecestat groups vs placebo. After stopping treatment, follow-up cognitive testing and AE assessment provided evidence of reversibility of drug-induced cognitive worsening and AEs in atabecestat groups.Atabecestat treatment was associated with dose-related cognitive worsening as early as 3 months and presence of neuropsychiatric treatment-emergent AEs, with evidence of reversibility after 6 months off treatment.ClinicalTrials.gov Identifier: NCT02569398.