tbuckley/cabot-search huggingface dataset:
Efficacy of Daratumumab, Lenalidomide, and Dexamethasone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma and Impaired Renal Function from the Phase 3 Maia Study Based on Lenalidomide Starting Dose
Authors: Saad Z. Usmani, Shaji Kumar, Torben Plesner, Robert Z. Orlowski, Philippe Moreau, Nizar J. Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael E. O'Dwyer, Aurore Perrot, Chris P. Venner, Katja Weisel, Joseph R. Mace, Noopur S. Raje, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Huiling Pei, Rian Van Rampelbergh, Brenda Tromp, Maria Delioukina, Thierry Facon
Journal: Blood (2021)
Development and Validation of a Long-Term Incident Heart Failure Risk Model
Authors: Sadiya S. Khan, Hongyan Ning, Norrina B. Allen, Mercedes R. Carnethon, Clyde W. Yancy, Sanjiv J. Shah, John T. Wilkins, Lu Tian, Donald M. Lloyd-Jones
Journal: Circulation Research (2021)

Average lifetime risk for heart failure (HF) is high but differs significantly across and within sex-race groups. No models for estimating long-term risk for HF exist, which would allow for earlier identification and interventions in high-risk subsets. The authors aim to derive 30-year HF risk equations.Adults between the ages of 20 to 59 years and free of cardiovascular disease at baseline from 5 population-based cohorts were included. Among 24 838 participants (55% women, 25% Black based on self-report), follow-up consisted of 599 551 person-years. Sex- and race-specific 30-year HF risk equations were derived and validated accounting for competing risk of non-HF death. HF was based on a clinical diagnosis. Model discrimination and calibration were assessed using 10-fold cross-validation. Finally, the model was applied to varying risk factor patterns for systematic examination.The rate of incident HF was 4.0 per 1000 person-years. Harrell C statistics were 0.82 (0.80-0.83) and 0.84 (0.82-0.85) in White and Black men and 0.84 (0.82-0.85) and 0.85 (0.83-0.87) in White and Black women, respectively. Hosmer-Lemeshow calibration was acceptable, with χ2 <30 in all subgroups. Risk estimation varied across sex-race groups: for example, in an average 40-year-old nonsmoker with an untreated systolic blood pressure of 140 mm Hg and body mass index of 30 kg/m2, risk was estimated to be 22.8% in a Black man, 13.7% in a White man, 13.0% in a Black woman, and 12.1% in a White woman.Sex- and race-specific equations for prediction of long-term risk of HF demonstrated high discrimination and adequate calibration.
The Intersection of Nativity With Race and Ethnicity in Preeclampsia—Broadening the Assessment of Social Determinants of Maternal Health
Authors: Nilay S. Shah, Kiarri N. Kershaw, Sadiya S. Khan
Journal: JAMA Network Open (2021)

Ellen Boakye, MD, MPH; Yaa Adoma Kwapong, MD, MPH; Olufunmilayo Obisesan, MD, MPH; S. Michelle Ogunwole, MD; Allison G. Hays, MD; Khurram Nasir, MD, MPH, MSc; Roger S. Blumenthal, MD; Pamela S. Douglas, MD; Michael J. Blaha, MD, MPH; Xiumei Hong, MD, PhD; Andreea A. Creanga, MD, PhD; Xiaobin Wang, MD, MPH, ScD; Garima Sharma, MD
Transthyretin V142I Genetic Variant and Cardiac Remodeling, Injury, and Heart Failure Risk in Black Adults
Authors: Amanda C. Coniglio, Matthew W. Segar, Rahul S. Loungani, Jainy J. Savla, Justin L. Grodin, Ervin R. Fox, Sonia Garg, James A. de Lemos, Jarett D. Berry, Mark H. Drazner, Sanjiv Shah, Michael E. Hall, Amil Shah, Sadiya S. Khan, Robert J. Mentz, Ambarish Pandey
Journal: JACC Heart Failure (2021)
Phase 1/1b Safety Study of Prgn-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes
Authors: David A. Sallman, Hany Elmariah, Kendra Sweet, Chetasi Talati, Asmita Mishra, Cheryl A Cox, Roshanak Semnani, Rutul R Shah, Helen Sabzevari, Marion Chakiath, Justin Uthuppan, Amy Lankford, Chen Wang, Eric Padron, Andrew T. Kuykendall, Rami S. Komrokji, Jeffrey E. Lancet, Marco L. Davila, Nelli Bejanyan
Journal: Blood (2021)
Abstract 16758: Unexplained Recurrent St-elevation Myocardial Infarction Complicated By Diffuse Alveolar Hemorrhage In Undiagnosed Granulomatosis With Polyangiitis
Authors: Juthipong Benjanuwattra, Poemlarp Mekraksakit, Mahmoud Abdelnabi
Journal: Circulation (2021)

Case Presentation: A 53-year-old man with a history of well-controlled hypertension and dyslipidemia presented with chest pain due to anterior STEMI for which a proximal LAD stent was placed. A week later, he presented with recurrent chest pain and ST elevation in the anterior chest leads. Coronary angiography showed in-stent thrombosis with heavy thrombus burden extending through the LAD. Manual thrombectomy with a second stent placement was done. He was discharged on triple therapy (aspirin, clopidogrel, and rivaroxaban), later, he presented to our medical facility with a 1-week history of hemoptysis. His clinical condition deteriorated requiring intubation. Laboratory work-up revealed elevated renal functions, proteinuria, and significant hematuria. CXR showed diffuse patchy opacities while CT chest was consistent with diffuse alveolar hemorrhage (Figure 1). Further work-up revealed elevated anti-proteinase 3 (c-ANCA) and low C4. Based on microscopic hematuria, renal impairment, and a positive c-ANCA, a diagnosis of granulomatosis with polyangiitis (GPA) was made. Induction with methylprednisolone, cyclophosphamide, and rituximab was initiated. His condition gradually improved, he was extubated successfully with marked improvement of renal functions. He was discharged on clopidogrel and scheduled for follow-up. Discussion: Few case reports have described STEMI as the initial presentation of GPA, likely attributed to vasculitis and accelerated atherosclerosis from systemic inflammation. Our patient had well-controlled cardiovascular risk factors and renal involvement with hematuria and elevated creatinine at the time of STEMI diagnosis, together with intermittent joint pains, suggesting ongoing systemic vasculitis. Clinicians should have a high index of suspicion for the possibility of non-atherosclerotic coronary stenosis as in cases of coronary vasculitis for early detection and management of a potentially reversible condition.
High MYC Expression Predicts Poor Survival Outcomes in IDH1/2 Mutant AML Patients
Authors: Virginia Olivia Volpe, Nicole D. Vincelette, Onyee Chan, Chetasi Talati, Kendra Sweet, Andrew T. Kuykendall, Constantine Logothetis, Rami S. Komrokji, Gregoire Calon, Nathan P. Horvat, David A. Sallman, Eric Padron, Ling Zhang, Seongseok Yun
Journal: Blood (2021)
Reimagining Rural: Shifting Paradigms About Health and Well-Being in the Rural United States
Authors: R.A. Afifi, E.A. Parker, G. Dino, D.M. Hall, B. Ulin
Journal: Annual Review of Public Health (2021)

Rural health disparities have attracted increased national attention, compelling an expanded focus on rural health research. In this article, we deconstruct the definitions and narratives of "rural" communities and suggest that a paradigm shift is needed that centers the complexity and strength of rural places. We discuss the relevance of health equity frameworks, implementation science, and community-engaged approaches to promote rural well-being. Focusing on rural in its own right will lead to intervention innovations and reinvention with implications beyond rural areas. We conclude with suggestions for research and practice to inspire renewed interest in partnering with rural communities to promote health equity.
Myocardial Fibrosis Quantified by Cardiac CT Predicts Outcome in Severe Aortic Stenosis After Transcatheter Intervention
Authors: Paul R. Scully, Kush P. Patel, Ernst Klotz, João B. Augusto, George D. Thornton, Bunny Saberwal, Ulrike Haberland, Simon Kennon, Muhiddin Ozkor, Michael Mullen, Guy Lloyd, Andrew Kelion, Leon J. Menezes, Philip N. Hawkins, James C. Moon, Francesca Pugliese, Thomas A. Treibel
Journal: JACC. Cardiovascular imaging (2021)
High Early Death Rates, Treatment Resistance and Short Survival of Black Adolescent and Young Adults (AYAs) with Acute Myeloid Leukemia (AML) (Alliance)
Authors: Karilyn Larkin, Deedra Nicolet, Ben Kelly, Krzysztof Mrózek, Katherine E Miller, Saranga Wijeratne, Stephanie LaHaye, Jessica Kohlschmidt, James S. Blachly, Alice S. Mims, Christopher J. Walker, Christopher C. Oakes, Shelley Orwick, Isaiah Boateng, Jill Buss, Adrienne Heyrosa, Andrew J Carroll, William Blum, Bayard L. Powell, Jonathan E Kolitz, Joseph O. Moore, Robert James Mayer, Richard A. Larson, Richard M. Stone, Electra D. Paskett, John C. Byrd, Elaine R. Mardis, Ann-Kathrin Eisfeld
Journal: Blood (2021)
Upper and lower respiratory tract correlates of protection against respiratory syncytial virus following vaccination of nonhuman primates
Authors: Tomer Zohar, Jeff C. Hsiao, Nickita Mehta, Jishnu Das, Anush Devadhasan, Wiktor Karpinski, Cheryl Callahan, Michael P. Citron, Daniel J. DiStefano, Sinoeun Touch, Zhiyun Wen, Jeffrey R. Sachs, Pedro J. Cejas, Amy S. Espeseth, Douglas A. Lauffenburger, Andrew J. Bett, Galit Alter
Journal: Cell Host & Microbe (2021)

Respiratory syncytial virus (RSV) infection is a major cause of respiratory illness in infants and the elderly. Although several vaccines have been developed, none have succeeded in part due to our incomplete understanding of the correlates of immune protection. While both T cells and antibodies play a role, emerging data suggest that antibody-mediated mechanisms alone may be sufficient to provide protection. Therefore, to map the humoral correlates of immunity against RSV, antibody responses across six different vaccines were profiled in a highly controlled nonhuman primate-challenge model. Viral loads were monitored in both the upper and lower respiratory tracts, and machine learning was used to determine the vaccine platform-agnostic antibody features associated with protection. Upper respiratory control was associated with virus-specific IgA levels, neutralization, and complement activity, whereas lower respiratory control was associated with Fc-mediated effector mechanisms. These findings provide critical compartment-specific insights toward the rational development of future vaccines.
Univariable associations between a history of incarceration and HIV and HCV prevalence among people who inject drugs across 17 countries in Europe 2006 to 2020 – is the precautionary principle applicable?
Authors: Lucas Wiessing, Eleni Kalamara, Jack Stone, Peyman Altan, Luk Van Baelen, Anastasios Fotiou, D’Jamila Garcia, Joao Goulao, Bruno Guarita, Vivian Hope, Marie Jauffret-Roustide, Lina Jurgelaitienė, Martin Kåberg, Adeeba Kamarulzaman, Liis Lemsalu, Anda Kivite-Urtane, Branko Kolarić, Linda Montanari, Magdalena Rosińska, Lavinius Sava, Ilonka Horváth, Thomas Seyler, Vana Sypsa, Anna Tarján, Ioanna Yiasemi, Ruth Zimmermann, Marica Ferri, Kate Dolan, Anneli Uusküla, Peter Vickerman
Journal: Eurosurveillance (2021)

BackgroundPeople who inject drugs (PWID) are frequently incarcerated, which is associated with multiple negative health outcomes.AimWe aimed to estimate the associations between a history of incarceration and prevalence of HIV and HCV infection among PWID in Europe.MethodsAggregate data from PWID recruited in drug services (excluding prison services) or elsewhere in the community were reported by 17 of 30 countries (16 per virus) collaborating in a European drug monitoring system (2006-2020; n = 52,368 HIV+/-; n = 47,268 HCV+/-). Country-specific odds ratios (OR) and prevalence ratios (PR) were calculated from country totals of HIV and HCV antibody status and self-reported life-time incarceration history, and pooled using meta-analyses. Country-specific and overall population attributable risk (PAR) were estimated using pooled PR.ResultsUnivariable HIV OR ranged between 0.73 and 6.37 (median: 2.1; pooled OR: 1.92; 95% CI: 1.52-2.42). Pooled PR was 1.66 (95% CI 1.38-1.98), giving a PAR of 25.8% (95% CI 16.7-34.0). Univariable anti-HCV OR ranged between 1.06 and 5.04 (median: 2.70; pooled OR: 2.51; 95% CI: 2.17-2.91). Pooled PR was 1.42 (95% CI: 1.28-1.58) and PAR 16.7% (95% CI: 11.8-21.7). Subgroup analyses showed differences in the OR for HCV by geographical region, with lower estimates in southern Europe.ConclusionIn univariable analysis, a history of incarceration was associated with positive HIV and HCV serostatus among PWID in Europe. Applying the precautionary principle would suggest finding alternatives to incarceration of PWID and strengthening health and social services in prison and after release ('throughcare').
Critical Escalation of de Novo Pediatric Anorexia Nervosa
Authors: Youngjung Kim
Journal: JAMA Network Open (2021)

Holly Agostino, MD, CM; Brett Burstein, MD, CM, PhD, MPH; Dina Moubayed, MD, CM; Danielle Taddeo, MD, CM; Rosheen Grady, MD; Ellie Vyver, MD; Gina Dimitropoulos, PhD, MSW; Anna Dominic, MD; Jennifer S. Coelho, PhD, RPsych
Abstract 11488: Ventilation Rate and Sustained Return of Spontaneous Circulation in In-Hospital Cardiac Arrest: Is More Better?
Authors: Ian S Jaffe, Eugene Yuriditsky, Tara Keshavarz Shirazi, Anelly Gonzales, James Horowitz, Sam Parnia
Journal: Circulation (2021)

Introduction: Current consensus holds that CPR must balance chest compressions and ventilation rate (VR), with a low VR being essential for venous return and cardiac output. AHA guidelines recommend a VR of 10 ventilations per minute (vpm) after advanced airway placement. We sought to examine VR adherence and its impact on end-tidal CO 2 (ETCO 2 ) and ROSC &gt;20 minutes. Methods: This is a retrospective analysis of data from AWARE II, a multicenter prospective observational study of adult in-hospital cardiac arrest (IHCA) outcomes at 14 US and UK sites. Inclusion criteria were: 1) adult patient in CA, 2) advanced airway already in place or placed during the CA, and 3) at least one minute of VR and ETCO 2 data available after removal of the last minute of CPR in subjects achieving ROSC (due to the rise of ETCO 2 just prior to ROSC). Results: A total of 563 subjects were enrolled in the parent study. Of these, 225 had ETCO 2 and VR tracings available, and 201 had sufficient data for inclusion. Mean age was 69.3 (range 18-100), patients were 63.7% male, and 16.4% had a shockable initial rhythm. A total of 116 subjects (57.7%) achieved ROSC, which was sustained in 76 (37.8%), leading to survival to hospital discharge with favorable neurological outcomes in 9 (4.5%). Mean VR was 16.3 vpm, with 171 (85.1%) subjects being ventilated in excess of guidelines; only 16 (8.0%) subjects received 8-10 vpm. Higher VR had a weak but significant association with increased mean ETCO 2 (linear R 2 = 0.11, p &lt; 1x10 -6 ) and sustained ROSC (OR 1.05; 95% CI: 1.01-1.11; p = 0.02). Patients with sustained ROSC had a significantly higher VR at 17.7 vpm than those without sustained ROSC at 15.6 vpm (p = 0.007). Patients receiving a VR close to AHA guidelines (6-12 vpm) had a significantly lower rate of sustained ROSC (26.1%, n = 46) than patients receiving &gt;12 vpm (42.0%, n = 148) (OR 2.30; 95% CI: 1.08-4.89; p = 0.031 using a multivariate model including patient age, shockable initial rhythm, known cardiac disease, witnessed IHCA, and use of mechanical compressions). Conclusions: VR within AHA guidelines is rare during IHCA. However, ventilation in excess of current guidelines may increase rates of sustained ROSC, an essential predicate to survival. AHA guidelines on VR in CPR with an advanced airway may not yet be optimized.
Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy–lysosomal pathway
Authors: Xiliang Du, Chiara Di Malta, Zhiyuan Fang, Taiyu Shen, Xiaodi Niu, Meng Chen, Bo Jin, Hao Yu, Lin Lei, Wenwen Gao, Yuxiang Song, Zhe Wang, Chuang Xu, Zhijun Cao, Guowen Liu, Xinwei Li
Journal: Acta Pharmaceutica Sinica B (2021)

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy–lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1–TFEB–ALP axis could represent a novel pharmacological strategy to combat NAFLD.
EXTH-57. EFFICACY OF SOLUBLE PANOBINOSTAT (MTX110) IN PRECLINICAL MODELS OF ADULT GLIOBLASTOMA
Authors: Greg Palmer, Stephen T Keir, David M Ashley, Rhian Davies, Ben Williams, Zoe Rees, Keith Laemont, Rafaela Belloni, Stephen J P Damment, Kelly Conlon
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION One of the biggest challenges in treating glioblastoma is achieving effective local drug concentrations, and trials using systemic administration of therapeutics have failed in GBM despite compelling pre-clinical evidence. MTX110 (Midatech Pharma PLC) is a water-soluble form of panobinostat currently in clinical development for DIPG and medulloblastoma using direct tumor delivery. We have previously reported a significant positive benefit of MTX110 in a subcutaneous GBM mouse model in an IDH1 mutated cell line. Here we present follow on data on the potential for MTX110 synergy with radiation in pre-clinical in vivo models. We also present data on efficacy of MTX110 in a panel of GBM cell lines. METHODS In vitro: Cell lines were incubated with MTX110 for 72h over a range of concentrations (1nM-10µM). Each concentration was tested in triplicate with the appropriate blank controls included in each plate. After 72 hours, cell viability was measured via luminescence signal (Promega CellTiter-Glo Luminescent Cell Viability Assay kit (Promega-G7573) read via 2104 EnVision Multilabel Reader, PerkinElmer. In vivo: Tumor-bearing mice were stratified to either the vehicle control or treatment group based on median tumor volume and were treated with MTX110 at a dose of 15mg/kg IP, 5 days consecutively for 2 consecutive weeks, following radiation treatment at a dose of 4Gy delivered as a single fraction on day 1. RESULTS In vitro, MTX110 demonstrated cytotoxic activity in 4 GBM cell lines (U87MG, U251MG, U118MG and T98G) with an average IC50 value in the region of 40nM (17-43nM). In vivo MTX110 in combination with radiation treatment showed an enhanced delay in tumor growth of approximately 50% compared to MTX110 or radiation alone. The results are supportive of the planned exploratory trial in GBM with MTX110.
Chlorthalidone in Advanced Chronic Kidney Disease — Have We Missed a Trick?
Authors: David C. Wheeler
Journal: New England Journal of Medicine (2021)

Control of hypertension is central to the management of chronic kidney disease, both to preserve residual kidney function and to reduce the associated high risk of cardiovascular events. International guidelines recently updated by the Kidney Disease: Improving Global Outcomes Organization recommend that patients with chronic kidney disease and hypertension be treated to reduce standardized office systolic blood pressure to less than 120 mm Hg, unless there are obvious reasons not to do so.1 This ambitious target is difficult to achieve with currently available antihypertensive medications, particularly in patients with more advanced chronic kidney disease (stages 4 and 5).2 In principle, . . .
Integrated Metabolic Profiling and Transcriptional Analysis Reveals Therapeutic Modalities for Targeting Rapidly Proliferating Breast Cancers
Authors: Chengheng Liao, Cherise Ryan Glodowski, Cheng Fan, Juan Liu, Kevin R. Mott, Akash Kaushik, Hieu Vu, Jason W. Locasale, Samuel K. McBrayer, Ralph J. DeBerardinis, Charles M. Perou, Qing Zhang
Journal: Cancer Research (2021)

Metabolic dysregulation is a prominent feature in breast cancer, but it remains poorly characterized in patient tumors. In this study, untargeted metabolomics analysis of triple-negative breast cancer (TNBC) and patient with estrogen receptor (ER)-positive breast cancer samples, as well as TNBC patient-derived xenografts (PDX), revealed two major metabolic groups independent of breast cancer histologic subtypes: a "Nucleotide/Carbohydrate-Enriched" group and a "Lipid/Fatty Acid-Enriched" group. Cell lines grown in vivo more faithfully recapitulated the metabolic profiles of patient tumors compared with those grown in vitro. Integrated metabolic and gene expression analyses identified genes that strongly correlate with metabolic dysregulation and predict patient prognosis. As a proof of principle, targeting Nucleotide/Carbohydrate-Enriched TNBC cell lines or PDX xenografts with a pyrimidine biosynthesis inhibitor or a glutaminase inhibitor led to therapeutic efficacy. In multiple in vivo models of TNBC, treatment with the pyrimidine biosynthesis inhibitor conferred better therapeutic outcomes than chemotherapeutic agents. This study provides a metabolic stratification of breast tumor samples that can guide the selection of effective therapeutic strategies targeting breast cancer subsets. In addition, we have developed a public, interactive data visualization portal (http://brcametab.org) based on the data generated from this study to facilitate future research.