tbuckley/cabot-search huggingface dataset:
Author Correction: Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias
Authors: Mahesh Raundhal, Shrestha Ghosh, Samuel A. Myers, Michael S. Cuoco, Meromit Singer, Steven A. Carr, Sushrut S. Waikar, Joseph V. Bonventre, Jerome Ritz, Richard M. Stone, David P. Steensma, Aviv Regev, Laurie H. Glimcher
Journal: Nature Immunology (2021)
P12.08 Efficacy of trazodone slow release in insomnia associated with high-dose steroid therapy in neuro-oncological patients
Authors: A Botturi, P Gaviani, V Redaelli, G Simonetti, C Lucchiari, A Silvani
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Insomnia linked to therapeutical intake of intravenous (IV) megadoses of steroid (Mgds, 8–16 mg) is a common side effect in neuro-oncology patients. Hypno-inducing drugs (IP) and Benzodiazepines (BDZ) can provoke drug interference and daytime sedation. Trazodone (Trz) is an atypical antidepressant with poor liver metabolism; it has moderate histamine-1 (H1) receptor antagonism and possesses some anxiolytic and hypnotic properties. We tested the use of the Trz retard (RP) formulation as a hypnotic drug in patients undergoing a therapeutic regimen with IV Mgds. To evaluate anxiety and side effects. MATERIAL AND METHODS 10 patients (6 females and 4 males) admitted to the Neuro-oncology Department of the Neurological Institute “Carlo Besta” treated with Mgds IV. The average age was 55 years and the mean HAM-A score was 25. Instruments included the Hamilton Anxiety Scale (HAM-A), the Clinical Global Impression (CGI), and the Pittsburgh Sleep Quality Index (PSQI). Trz RP was administered at a dosage of 25-50-75 mg/day in the evening. RESULTS All 10 patients reported improved hypnotic profiles within the third day of Trz RP administration. Four patients improved on the first day. Reduction of the HAM-A score was found on the third day. No adverse events (epilepsy, daytime sedation, incontinence) were observed in 3 weeks. CONCLUSIONS Trz RP proved to have a swift beneficial effect on sleep and anxiety without side effects in the short term. Trz may be preferred to IP and BDZ in patients receiving IV Mgds, considering the lack of daytime sedation and the reduced pharmacological inference. Larger samples will enable future research to better describe the characteristics and the indication of Trz.
Association of Myocardial Blood Flow Reserve With Adverse Left Ventricular Remodeling in Patients With Aortic Stenosis
Authors: Wunan Zhou, Yee-Ping Sun, Sanjay Divakaran, Navkaranbir S. Bajaj, Ankur Gupta, Alvin Chandra, Victoria Morgan, Leanne Barrett, Laurel Martell, Courtney F. Bibbo, Jon Hainer, Eldrin F. Lewis, Viviany R. Taqueti, Sharmila Dorbala, Ron Blankstein, Piotr Slomka, Pinak B. Shah, Tsuyoshi Kaneko, Dale S. Adler, Patrick O’Gara, Marcelo F. Di Carli
Journal: JAMA Cardiology (2021)

Impaired myocardial flow reserve (MFR) and stress myocardial blood flow (MBF) on positron emission tomography (PET) myocardial perfusion imaging may identify adverse myocardial characteristics, including myocardial stress and injury in aortic stenosis (AS).To investigate whether MFR and stress MBF are associated with LV structure and function derangements, and whether these parameters improve after aortic valve replacement (AVR).In this single-center prospective observational study in Boston, Massachusetts, from 2018 to 2020, patients with predominantly moderate to severe AS underwent ammonia N13 PET myocardial perfusion imaging for myocardial blood flow (MBF) quantification, resting transthoracic echocardiography (TTE) for assessment of myocardial structure and function, and measurement of circulating biomarkers for myocardial injury and wall stress. Evaluation of health status and functional capacity was also performed. A subset of patients underwent repeated assessment 6 months after AVR. A control group included patients without AS matched for age, sex, and summed stress score who underwent symptom-prompted ammonia N13 PET and TTE within 90 days.MBF and MFR quantified on ammonia N13 PET myocardial perfusion imaging.LV structure and function parameters, including echocardiographic global longitudinal strain (GLS), circulating high-sensitivity troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), health status, and functional capacity.There were 34 patients with AS (1 mild, 9 moderate, and 24 severe) and 34 matched control individuals. MFR was independently associated with GLS and LV ejection fraction, (β,-0.31; P = .03; β, 0.41; P = .002, respectively). Stress MBF was associated with hs-cTnT (unadjusted β, -0.48; P = .005) and log NT-pro BNP (unadjusted β, -0.37; P = .045). The combination of low stress MBF and high hs-cTnT was associated with higher interventricular septal thickness in diastole, relative wall thickness, and worse GLS compared with high stress MBF and low hs-cTnT (12.4 mm vs 10.0 mm; P = .008; 0.62 vs 0.46; P = .02; and -13.47 vs -17.11; P = .006, respectively). In 9 patients studied 6 months after AVR, mean (SD) MFR improved from 1.73 (0.57) to 2.11 (0.50) (P = .008).In this study, in AS, MFR and stress MBF were associated with adverse myocardial characteristics, including markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation.
Association of Nursing Home Characteristics With Staff and Resident COVID-19 Vaccination Coverage
Authors: Brian E. McGarry, Karen Shen, Michael L. Barnett, David C. Grabowski, Ashvin D. Gandhi
Journal: JAMA Internal Medicine (2021)

With Staff and Resident COVID-19 Vaccination CoverageVaccines have been instrumental in reducing COVID-19 cases and related deaths among US nursing home residents. 1However, low vaccination coverage among nursing home staff, 2 who may introduce COVID-19 into facilities, could contribute to future outbreaks, especially in the presence of more transmissible variants. 3,4 Maximizing vaccination coverage among nursing home staff and residents is critical because of the extreme vulnerability of this population to COVID-19, but little is known about which nursing homes have been successful at achieving high vaccination coverage.
Single-Cell Profiling Reveals Metabolic Reprogramming as a Resistance Mechanism in<i>BRAF</i>-Mutated Multiple Myeloma
Authors: Johannes M. Waldschmidt, Jake A. Kloeber, Praveen Anand, Julia Frede, Antonis Kokkalis, Valeriya Dimitrova, Sayalee Potdar, Monica S. Nair, Tushara Vijaykumar, Nam Gyu Im, Amy Guillaumet-Adkins, Nitish Chopra, Hannah Stuart, Lillian Budano, Noori Sotudeh, Guangwu Guo, Clemens Grassberger, Andrew J. Yee, Jacob P. Laubach, Paul G. Richardson, Kenneth C. Anderson, Noopur S. Raje, Birgit Knoechel, Jens G. Lohr
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Although remarkably effective in some patients, precision medicine typically induces only transient responses despite initial absence of resistance-conferring mutations. Using BRAF-mutated myeloma as a model for resistance to precision medicine we investigated if BRAF-mutated cancer cells have the ability to ensure their survival by rapidly adapting to BRAF inhibitor treatment. Experimental Design: Full-length single-cell RNA (scRNA) sequencing (scRNA-seq) was conducted on 3 patients with BRAF-mutated myeloma and 1 healthy donor. We sequenced 1,495 cells before, after 1 week, and at clinical relapse to BRAF/MEK inhibitor treatment. We developed an in vitro model of dabrafenib resistance using genetically homogeneous single-cell clones from two cell lines with established BRAF mutations (U266, DP6). Transcriptional and epigenetic adaptation in resistant cells were defined by RNA-seq and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq). Mitochondrial metabolism was characterized by metabolic flux analysis. Results: Profiling by scRNA-seq revealed rapid cellular state changes in response to BRAF/MEK inhibition in patients with myeloma and cell lines. Transcriptional adaptation preceded detectable outgrowth of genetically discernible drug-resistant clones and was associated with widespread enhancer remodeling. As a dominant vulnerability, dependency on oxidative phosphorylation (OxPhos) was induced. In treated individuals, OxPhos was activated at the time of relapse and showed inverse correlation to MAPK activation. Metabolic flux analysis confirmed OxPhos as a preferential energetic resource of drug-persistent myeloma cells. Conclusions: This study demonstrates that cancer cells have the ability to rapidly adapt to precision treatments through transcriptional state changes, epigenetic adaptation, and metabolic rewiring, thus facilitating the development of refractory disease while simultaneously exposing novel vulnerabilities.
Systematic review with meta-analysis: Non-alcoholic fatty liver disease and the association with pregnancy outcomes
Authors: Hydar El Jamaly, Guy D Eslick, Martin Weltman
Journal: Clinical and Molecular Hepatology (2021)

Maternal and fetal outcomes in pregnant patients with Non-alcoholic fatty liver disease (NAFLD) have been largely unexplored. To determine the level of evidence associated with maternal and fetal outcomes in pregnant women with NAFLD.We conducted a comprehensive literature search. The studies included pregnant patients with a previous, current or subsequent diagnosis of NAFLD. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI).Twenty-two studies, with 13,641 female NAFLD patients were reviewed. The results highlight that NAFLD patients had a statistically significant increased likelihood of baseline diabetes mellitus (OR, 6.00; 95% CI, 2.21-16.31; P<0.001; n=7), baseline Hypertension (OR, 3.75; 95% CI, 2.13-6.59; P<0.001; n=4), gestational hypertension (OR, 1.83; 95% CI, 1.03-3.26; P=0.041; n=2), and pre-eclampsia (OR, 2.43; 95% CI, 1.46-4.04; P=0.001; n=3). The odds for a past and current history of gestational diabetes mellitus were OR, 3.78; 95% CI, 2.21-6.44; P<0.001; n=5 and OR, 3.23; 95% CI, 1.97- 5.31; P<0.001; n=6, respectively. As for fetal outcomes, pregnant NAFLD patients were significantly more likely to have a premature birth (OR, 2.02; 95% CI, 1.44-2.85; P<0.001; n=4), large for gestational age birth (OR, 2.01; 95% CI, 1.72-2.37; P<0.001; n=2) or a history of prior miscarriage or abortion (OR, 1.15; 95% CI, 1.02-1.30; P=0.02; n=2). Egger's regression revealed no evidence of publication bias (P>0.05).This meta-analysis provides pooled evidence that NAFLD is associated with a substantial increase in maternal diabetic and hypertensive complications and multiple adverse fetal outcomes. This data is important for clinicians managing these patients before, during and after pregnancy.
Addressing alert fatigue by reducing radiation oncology software alert volume.
Authors: Itai Max Pashtan, Tara Kosak, Kevin Beaudette, Amy Buckman, Abigail Clark, Jill Connolly, Lynne Hicks, Julie Hudson, Rose Ribok, Ann Marie Ricciarelli, Kelly Scholl, Candy Zanelli, Meghan Kearney, Raymond H. Mak
Journal: Journal of Clinical Oncology (2021)

261 Background: Radiation therapists (RTTs) administer radiation treatments to patients with cancer. Treatments are delivered using linear accelerators (LINACs), operated by vendor specific software. Prior to delivering treatment, RTTs perform a time-out, and read aloud critical electronic communications (alerts) entered by members of the radiation oncology care team. Alerts are effective at communicating critical information, including treatment setup and imaging instructions, but can become a source of error due to alert fatigue when placed indiscriminately. Methods: A multicenter retrospective review of alert use per patient was conducted in 4 radiation oncology centers with a total of 6 LINACs. Alert usage was reviewed pre-intervention for 40 randomly selected patients using manual chart review. Each alert was reviewed for frequency and utilization. In attempt of improving communication and reducing alert fatigue, a multidisciplinary process improvement working group (with Radiation Oncologists, RTTs, nursing, physicists, and administration) was formed to review the utilization of alerts in our department and propose interventions. Three months after intervention, an additional 40 chart review was performed. Our aim was to reduce the volume of alerts by 20% within 3 months. A 2-tail t-test was used for statistical analysis. Results: Process improvements were implemented to reduce the volume of alerts per patient. Interventions included 1) defining an alert for all departmental staff, 2) creating guidelines for appropriate utilization of alerts, 3) routing communications not critical to RTTs at the time of radiation treatment administration through other channels, and 4) training staff as to the above. The pre-intervention review yielded 239 alerts. Post-intervention, there were 173 alerts, a reduction of 27% (p =.008). Conclusions: This practice change reduced average alert volume by 27%. As a result, alerts which are critical to safe treatment delivery by RTTs (i.e. daily setup alerts), became more heavily represented. Other alerts, which could be communicated effectively in other ways (i.e. OTVs [weekly on treatment visit with Radiation Oncologist]), were eliminated. By decreasing alert volume, the risk of RTT alert fatigue is reduced, communication improved, and treatment safety enhanced.[Table: see text]
All-trans retinoic acid plus high-dose dexamethasone as first-line treatment for patients with newly diagnosed immune thrombocytopenia: a multicentre, open-label, randomised, controlled, phase 2 trial
Authors: Qiu-Sha Huang, Yi Liu, Jing-Bo Wang, Jun Peng, Ming Hou, Hui Liu, Ru Feng, Jing-Wen Wang, Lan-Ping Xu, Yang Wang, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: The Lancet Haematology (2021)
Age and blood pressure stratified effects of blood pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual-level meta-analysis of 358,707 randomised participants
Authors: R Mcmanus, K Rahimi, Z Bidel Taleshmekaeil, M Nazarzadeh Larzjan, E Copland, D Canoy, J Majert
Journal: The Lancet (2021)
P-175 Effectiveness, prognostic factors and safety concerning ablative techniques in liver metastases from gastrointestinal tumors
Authors: M. Gomez-Randulfe Rodriguez, B. Alonso de Castro, E. Castro Lopez, M. Maestro Duran, S. Silva Diaz, C. Reboredo Rendo, B. Graña Suarez, M. Reboredo-Lopez, F. Perez Fontan, N. Martínez Lago
Journal: Annals of Oncology (2021)
Association of enteropathogen detection with diarrhoea by age and high versus low child mortality settings: a systematic review and meta-analysis
Authors: Julia M Baker, Mateusz Hasso-Agopsowicz, Virginia E Pitzer, James A Platts-Mills, Andre Peralta-Santos, Catherine Troja, Helena Archer, Boya Guo, William Sheahan, Jairam Lingappa, Mark Jit, Benjamin A Lopman
Journal: The Lancet Global Health (2021)

BackgroundThe odds ratio (OR) comparing pathogen presence in diarrhoeal cases versus asymptomatic controls is a measure for diarrhoeal disease cause that has been integrated into burden of disease estimates across diverse populations. This study aimed to estimate the OR describing the association between pathogen detection in stool and diarrhoea for 15 common enteropathogens by age group and child mortality setting.MethodsWe did a systematic review to identify case-control and cohort studies published from Jan 1, 1990, to July 9, 2019, which examined at least one enteropathogen of interest and the outcome diarrhoea. The analytical dataset included data extracted from published articles and supplemented with data from the Global Enteric Multicenter Study and the Malnutrition and Enteric Disease study. Random effects meta-analysis models were fit for each enteropathogen, stratified by age group and child mortality level, and adjusted for pathogen detection method and study design to produce summary ORs describing the association between pathogen detection in stool and diarrhoea.Findings1964 records were screened and 130 studies (over 88 079 cases or diarrhoea samples and 135 755 controls or non-diarrhoea samples) were available for analysis. Heterogeneity (I2) in unadjusted models was substantial, ranging from 27·6% to 86·6% across pathogens. In stratified and adjusted models, summary ORs varied by age group and setting, ranging from 0·4 (95% CI 0·2–0·6) for Giardia lamblia to 54·1 (95% CI 7·4–393·5) for Vibrio cholerae.InterpretationIncorporating effect estimates from diverse data sources into diarrhoeal disease cause and burden of disease models is needed to produce more representative estimates.FundingWHO, Bill & Melinda Gates Foundation, and National Institutes of Health.
HLA Allele–Restricted Immune-Mediated Adverse Drug Reactions: Framework for Genetic Prediction
Authors: Kanoot Jaruthamsophon, Paul J. Thomson, Chonlaphat Sukasem, Dean J. Naisbitt, Munir Pirmohamed
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Human leukocyte antigen (HLA) is a hallmark genetic marker for the prediction of certain immune-mediated adverse drug reactions (ADRs). Numerous basic and clinical research studies have provided the evidence base to push forward the clinical implementation of HLA testing for the prevention of such ADRs in susceptible patients. This review explores current translational progress in using HLA as a key susceptibility factor for immune ADRs and highlights gaps in our knowledge. Furthermore, relevant findings of HLA-mediated drug-specific T cell activation are covered, focusing on cellular approaches to link genetic associations to drug-HLA binding as a complementary approach to understand disease pathogenesis.
Results of the Swiss Multicenter Intracoronary Stem Cells Study in Acute Myocardial Infarction (Swiss Ami) Trial
Authors: Suerder Daniel, Manka Robert, Moccetti Tiziano, Rufibach Kaspar, Astori Giuseppe, Cicero Viviano Lo, Soncin Sabrina, Turchetto Lucia, Radrizzani Marina, Windecker Stephan, Moschovitis Aris, Wahl Andreas, Erne Paul, Der Maur Christoph Auf, Soldati Gianni, Buehler Ines, Wyss Christophe, Schwitter Juerg, Landmesser Ulf, F Luescher Thomas, Corti Roberto
Journal: Circulation (2012)
P-72 A patient preference study on risk thresholds to switch between daily tablets and biweekly infusions in second-line treatment for advanced hepatocellular carcinoma
Authors: N. Parikh, A. Girvan, J. Coulter, J. Gable, J. Poon, S. Kim, A. Chatterjee, M. Boeri
Journal: Annals of Oncology (2021)
Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis
Authors: Alessandro Mantovani, Alessandro Csermely, Graziana Petracca, Giorgia Beatrice, Kathleen E Corey, Tracey G Simon, Christopher D Byrne, Giovanni Targher
Journal: The Lancet. Gastroenterology & hepatology (2021)
Of bats and men: Immunomodulatory treatment options for COVID-19 guided by the immunopathology of SARS-CoV-2 infection
Authors: Michael J. Christie, Aaron T. Irving, Samuel C. Forster, Benjamin J. Marsland, Philip M. Hansbro, Paul J. Hertzog, Claudia A. Nold-Petry, Marcel F. Nold
Journal: Science Immunology (2021)

In humans, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is highly infective, often causes severe acute and/or long-term illness, and elicits a high rate of mortality, even in countries with sophisticated medical systems. Detailed knowledge on the immune responses underpinning COVID-19 (coronavirus disease 2019), and on strategies SARS-CoV-2 uses to evade them, can provide pivotal guidance to researchers and clinicians developing and administering potentially life-saving immunomodulatory therapies. The need for such therapies in COVID-19 is unlikely to abate soon given the emergence of variants of concern that may pose new challenges for some vaccines and neutralizing antibodies. Here, we summarize current knowledge on COVID-19 immunopathogenesis in relation to three clinical disease stages and focus on immune evasion strategies used by pathogenic coronaviruses such as skewing type I, II, and III interferon responses and inhibiting detection via pattern recognition and antigen presentation. Insights gained from bats, which exhibit minimal disease in response to SARS-CoV-2 infection, offer an informative perspective and may guide future development of new therapies. We also discuss how knowledge of immunopathology may inform therapeutic decisions, for example, on selecting the most appropriate immunotherapeutic agents and timing their administration, to reduce morbidity and mortality of COVID-19.
Randomized Controlled Trial of a Dichoptic Digital Therapeutic for Amblyopia
Authors: Scott Xiao, Endri Angjeli, Hank C. Wu, Eric D. Gaier, Stephanie Gomez, Dean A. Travers, Gil Binenbaum, Robert Langer, David G. Hunter, Michael X. Repka
Journal: Ophthalmology (2021)

Digital therapeutics are a new class of interventions that are software driven and are intended to treat various conditions. We developed and evaluated a dichoptic digital therapeutic for amblyopia, a neurodevelopmental disorder for which current treatments may be limited by poor adherence and residual vision deficits.Randomized controlled trial.One hundred five children 4 to 7 years of age with amblyopia were enrolled at 21 academic and community sites in the United States. Participants were randomized 1:1 to the treatment or comparison group, stratified by site.We conducted a phase 3 randomized controlled trial to evaluate the safety and efficacy of a dichoptic digital therapeutic for amblyopia. Participants in the treatment group used the therapeutic at home for 1 hour per day, 6 days per week and wore glasses full-time. Participants in the comparison group continued wearing glasses full-time alone.The primary efficacy outcome was change in amblyopic eye visual acuity (VA) from baseline at 12 weeks, and VA was measured by masked examiners. Safety was evaluated using the frequency and severity of study-related adverse events. Primary analyses were conducted using the intention-to-treat population.Between January 16, 2019, and January 15, 2020, 105 participants were enrolled; 51 were randomized to the treatment group and 54 were randomized to the comparison group. At 12 weeks, amblyopic eye VA improved by 1.8 lines (95% confidence interval [CI], 1.4-2.3 lines; n = 45) in the treatment group and by 0.8 lines (95% CI, 0.4-1.3 lines; n = 45) in the comparison group. At the planned interim analysis (adjusted α = 0.0193), the difference between groups was significant (1.0 lines; P = 0.0011; 96.14% CI, 0.33-1.63 lines) and the study was stopped early for success, according to the protocol. No serious adverse events were reported.Our findings support the value of the therapeutic in clinical practice as an effective treatment. Future studies should evaluate the therapeutic compared with other methods and in additional patient populations.