tbuckley/cabot-search huggingface dataset:
Type I interferon signature predicts response to JAK inhibition in haploinsufficiency of A20
Authors: Daniella Muallem Schwartz, Sarah A Blackstone, Natalia Sampaio-Moura, Sofia Rosenzweig, Aarohan M Burma, Deborah Stone, Patrycja Hoffmann, Anne Jones, Tina Romeo, Karyl S Barron, Meryl A Waldman, Ivona Aksentijevich, Daniel L Kastner, Joshua D Milner, Amanda K Ombrello
Journal: Annals of the Rheumatic Diseases (2019)

The anti-inflammatory protein A20, encoded by TNFAIP3 , is a ubiquitin-modifying enzyme that targets proinflammatory molecules, including those upstream of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Patients with heterozygous loss-of-function TNFAIP3 mutations develop haploinsufficiency of A20 (HA20), a systemic autoinflammatory disease that can cause severe end-organ pathology.1–3 No available medication directly targets NF-κB signalling; thus, treatment decisions are based on clinical experience. Mild cases are treated with disease-modifying antirheumatic drugs, whereas severe cases are treated with systemic corticosteroids and biological agents, including tumour necrosis factor (TNF)-α and IL-1 receptor (IL-1R) blockade.1 2 We report that a type I interferon (IFN) signature, or elevation of IFN-stimulated genes (ISGs), correlates with disease activity and predicts response to janus kinase (JAK) inhibition in HA20.

A cohort of 12 patients with HA20 is followed at the NIH Clinical Center. All patients were diagnosed by Sanger sequencing, and increased NF-κB activity was confirmed with luciferase assay.2 Five patients had disease that was treatment-refractory or caused end-organ pathology. P1 was a 15-year-old female with p.T604Rfs*93 and severe gastrointestinal ulcerations refractory to TNF-α and IL-1R inhibition. P2–P4 were members of the same extended family with p.F224Sfs*4, aged 28, 32 and 61 years. All three had incomplete responses to TNF-α and IL-1R blockade; P2 had retinal vasculopathy and neuroinflammation, whereas P3 had membranous nephropathy. …
Machine learning can accurately predict pre-admission baseline hemoglobin and creatinine in intensive care patients
Authors: Antonin Dauvin, Carolina Donado, Patrik Bachtiger, Ke-Chun Huang, Christopher Martin Sauer, Daniele Ramazzotti, Matteo Bonvini, Leo Anthony Celi, Molly J. Douglas
Journal: npj Digital Medicine (2019)

Abstract Patients admitted to the intensive care unit frequently have anemia and impaired renal function, but often lack historical blood results to contextualize the acuteness of these findings. Using data available within two hours of ICU admission, we developed machine learning models that accurately (AUC 0.86–0.89) classify an individual patient’s baseline hemoglobin and creatinine levels. Compared to assuming the baseline to be the same as the admission lab value, machine learning performed significantly better at classifying acute kidney injury regardless of initial creatinine value, and significantly better at predicting baseline hemoglobin value in patients with admission hemoglobin of &lt;10 g/dl.
Therapeutic Advances in First-Line Management of Acute Myeloid Leukemia
Authors: Daniel A. Pollyea
Journal: Journal of the National Comprehensive Cancer Network (2019)

Over the past several years, drug approvals for first-line treatment of acute myeloid leukemia have changed the landscape from a "wasteland" to an "embarrassment of riches." In general, patients deemed "fit" for induction chemotherapy who have a core-binding factor abnormality should receive 7 + 3 in combination with gemtuzumab, 7 + 3 with midostaurin for those with an FLT3 abnormality, and liposomal cytarabine + daunorubicin for patients with secondary AML. Although other options exist, Dr. Daniel A. Pollyea recommended a venetoclax/azacitidine regimen for newly diagnosed "unfit" patients. Future research should focus on more clearly determining the definition of a "fit" patient, he said at the NCCN 2019 Annual Congress: Hematologic Malignancies.
Generalizability of national survival estimates to adolescent and young adults with cancer at an urban safety-net institution.
Authors: Aaron Gehr, Yan Lu, Bassam Ghabach, Rohit P. Ojha
Journal: Journal of Clinical Oncology (2019)

140 Background: Survival estimates for adolescent and young adults (AYAs) with cancer in the US are largely derived from the Surveillance, Epidemiology, and End Results (SEER) program, which does not include certain geographic areas with diverse populations such as Texas. The generalizability of these estimates to other populations is unknown but may be useful for identifying high-risk populations. Therefore, we aimed to assess the generalizability of survival estimates for AYAs with cancer in SEER to AYAs with cancer at an urban safety-net institution in Texas. Methods: We used data from the SEER program and the JPS Oncology and Infusion Center, an accredited Comprehensive Community Cancer Program. Eligible individuals in both populations were aged 18 – 39 years and diagnosed with a first primary cancer between 2008 and 2015. We computed entropy-balanced weights to adjust the baseline distribution of age, gender, race/ethnicity, insurance status, marital status, cancer type, and stage of the SEER population to our safety-net population. We used these weights to compute Kaplan-Meier estimates of expected survival for our safety-net population. We subsequently estimated the absolute survival difference between expected and observed (i.e. actual) survival and corresponding 95% confidence limits (CL). Results: Our safety-net population comprised 833 AYAs with cancer, of whom 60% were female, 62% were racial/ethnic minorities, and 66% were uninsured at diagnosis. The most common cancers were hematologic (17%), female genital (16%), thyroid (11%), and breast (11%). Metastasis was observed at diagnosis for 24% of AYAs. The expected 5-year survival for the safety-net population based on SEER data was 77%, whereas observed survival was 68%, which equated to an absolute survival difference of 9.5% (95% CL: 5.3%, 14%) after 5 years. Conclusions: Our results suggest that survival estimates of AYAs with cancer in SEER may not be generalizable to AYAs with cancer at an urban safety-net institution in Texas. Lack of generalizability may be relevant to other populations not represented in SEER. The reasons for poor survival of AYAs with cancer at safety-net institutions should be explored.
Setting up breast services improvements and learning bridges in Kyrgyzstan: The SILK project
Authors: O. Pagani, M. Del Grande, F. Peccatori, C. de Wolf, G. Pruneri, L. Mattei, A. Richetti, S. Presilla, T. Sabyrbekova, N. Bakirova, T. Soldak, D. Abdyldaev, T. Abdyldaev, I. Aliev, R. Aralbaev, S. Naizabekova, B. Shaimurzaeva, O. Shimkina, R. Marti, F. Cavalli
Journal: Annals of Oncology (2019)
Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile
Authors: Brian Skaug, Dinesh Khanna, William R Swindell, Monique E Hinchcliff, Tracy M Frech, Virginia D Steen, Faye N Hant, Jessica K Gordon, Ami A Shah, Lisha Zhu, W Jim Zheng, Jeffrey L Browning, Alexander M S Barron, Minghua Wu, Sudha Visvanathan, Patrick Baum, Jennifer M Franks, Michael L Whitfield, Victoria K Shanmugam, Robyn T Domsic, Flavia V Castelino, Elana J Bernstein, Nancy Wareing, Marka A Lyons, Jun Ying, Julio Charles, Maureen D Mayes, Shervin Assassi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Objectives</h3> Determine global skin transcriptome patterns of early diffuse systemic sclerosis (SSc) and how they differ from later disease. <h3>Methods</h3> Skin biopsy RNA from 48 patients in the Prospective Registry for Early Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and 33 matched healthy controls was examined by next-generation RNA sequencing. Data were analysed for cell type-specific signatures and compared with similarly obtained data from 55 previously biopsied patients in Genetics versus Environment in Scleroderma Outcomes Study cohort with longer disease duration (mean 7.4 years) and their matched controls. Correlations with histological features and clinical course were also evaluated. <h3>Results</h3> SSc patients in PRESS had a high prevalence of M2 (96%) and M1 (94%) macrophage and CD8 T cell (65%), CD4 T cell (60%) and B cell (69%) signatures. Immunohistochemical staining of immune cell markers correlated with the gene expression-based immune cell signatures. The prevalence of immune cell signatures in early diffuse SSc patients was higher than in patients with longer disease duration. In the multivariable model, adaptive immune cell signatures were significantly associated with shorter disease duration, while fibroblast and macrophage cell type signatures were associated with higher modified Rodnan Skin Score (mRSS). Immune cell signatures also correlated with skin thickness progression rate prior to biopsy, but did not predict subsequent mRSS progression. <h3>Conclusions</h3> Skin in early diffuse SSc has prominent innate and adaptive immune cell signatures. As a prominently affected end organ, these signatures reflect the preceding rate of disease progression. These findings could have implications in understanding SSc pathogenesis and clinical trial design.
Bernhoven approach is more than just patient centred care and shared decision making
Authors: Louisa Polak
Journal: BMJ (2019)

I enjoyed Venhuizen’s article about Bernhoven Hospital’s patient centred approach but have two criticisms.1

First, saying that “money is no longer an important incentive” in the intervention programme seems at odds with much of the rest of the article, including its title. Such statements reinforce an unhelpfully squeamish narrative about money—what is wrong with admitting that money is one of several …
A clash of <i>Umwelts</i>: Anthropomorphism in behavioral neuroscience
Authors: Alex Gomez-Marin
Journal: Behavioral and Brain Sciences (2019)

Abstract Brains enjoy a bodily life. Therefore animals are subjects with a point of view. Yet, coding betrays an anthropomorphic bias: we can, therefore they must. Here I propose a reformulation of Brette's question that emphasizes organismic perception, cautioning for misinterpretations based on external ideal-observer accounts. Theoretical ethology allows computational neuroscience to understand brains from the perspective of their owners.
Crizanlizumab 5.0 Mg/Kg Exhibits a Favorable Safety Profile in Patients with Sickle Cell Disease: Pooled Data from Two Phase II Studies
Authors: Julie Kanter, Darla K Liles, Kim Smith-Whitley, Clark Brown, Abdullah Kutlar, Brian Elliott, Amit Shah, Jeremie Lincy, Susan Poggio, Kenneth I. Ataga
Journal: Blood (2019)
Positive Airway Pressure in Obesity Hypoventilation: Getting to the Heart of the Matter
Authors: Amanda J. Piper, Edmund M. Lau
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

heavily on IPF; however, targeted studies analyzing rheumatoid arthritis-associated ILD and chronic hypersensitivity pneumonitis suggest that the prevalence of both MUC5B promoter polymorphism (16,17) and rare variants in telomere-related genes is similar to that observed in IPF (18,19).The most powerful insights that could come from future genetic studies in ILD would be links between genetic risk factors and specific ILD features or phenotypes.Such studies will require large and diverse cohorts, high-resolution phenotyping, and high-quality longitudinal data.This study by Allen and colleagues gives us reason to be optimistic that the large-scale collaborative efforts required for such investigations may be possible in the near future.
Enhancement of reactive oxygen species production by ceramide in RAW 264.7 murine macrophage activated with lipopolysaccharide and interferon-γ
Authors: Roger Sebastien, Pierre Besson, Philippe Bougnoux, Jean-Yves Leguennec
Journal: Cancer Research (2004)

866  Membrane potential and ion channels are usually studied in excitable cells. However, they appear to be involved in an increasing number of cell functions and in different pathologies. Their involvement in cell proliferation as well as in tumour invasiveness was demonstrated in several cancers. In breast cancer, the role of ion channels has been known since the work of Marino et al. in 1994 (1). Since this pioneer work, the role of ionic channels in breast cancer cell lines focused mainly on potassium channels (2, 3). The expression and the role of these channels in cell proliferation have been studied and at least 4 types of potassium channels exist in one of the most studied cell line, MCF-7 (3-5). These potassium channels are: KATP, Kv 1.1, hEAG and KCa. In the present study, we electrophysiologically investigated, by the whole-cell configuration of the patch-clamp technique, four human breast cancer cell lines: MCF-7, MDA-MB-231, MDA-MB-435s and MDA-MB-468. In all cell lines tested, we found a large-conductance, iberiotoxin-sensitive (IbTx), Ca2+-activated K+ channel (BKCa). This IbTx-sensitive conductance is increased by the Ca2+ sensitizer NS-1619. The blockade of this current by the specific blocker IbTx and its sensitization to Ca2+ by NS-1619 did not interfere with proliferation. In most tissues, this channel is well known as a key regulator of neuronal excitability, secretion, and vascular tone, by its ability to sense membrane depolarisation and increased intracellular Ca2+. Its stimulation results in an hyperpolarizing K+ current that reduces excitability. The cell lines we studied are from epithelial origin and are not excitable. Nevertheless this current has been suggested to be involved in the proliferation process of MCF-7 breast cancer cells (2, 4). From this study, we conclude that the IbTx-sensitive current, which is not involved in proliferation, is expressed in all the breast cancer cell lines studied. This suggests that this ion channel is probably expressed in normal epithelial cells and not involved in the oncogenic process. 1. A. A. Marino et al., Tumour Biol 15, 82-9 (1994). 2. J. S. Strobl, W. F. Wonderlin, D. C. Flynn, Gen Pharmacol 26, 1643-9 (Dec, 1995). 3. H. Ouadid-Ahidouch et al., Receptors Channels 7, 345-56 (2001). 4. E. A. Wegman, J. A. Young, D. I. Cook, Pflugers Arch 417, 562-70 (Feb, 1991). 5. E. Klimatcheva, W. F. Wonderlin, J Membr Biol 171, 35-46 (Sep 1, 1999).
The Evaluation and Treatment (Tx) of Burkitt Lymphoma (BL) in the Modern Era: Real World (RW) Outcomes and Prognostication across 26 US Cancer Centers (CC)
Authors: Andrew M. Evens, Alexey Danilov, Deepa Jagadeesh, Amy Sperling, Seo-Hyun Kim, Ryan Vaca, Catherine Wei, Daniel Rector, Suchitra Sundaram, Nishitha Reddy, Yong Lin, Umar Farooq, Christopher D'Angelo, David A. Bond, Stephanie Berg, Michael C. Churnetski, Amandeep Godara, Nadia Khan, Yun Kyong Choi, Maryam Yazdy, Emma Rabinovich, Gaurav Varma, Reem Karmali, Agrima Mian, Jeremy Ramdial, Madelyn Burkart, Peter Martin, Albert Ren, Ayushi Chauhan, Catherine Diefenbach, Allandria Straker-Edwards, Andreas Klein, Kristie A. Blum, Kirsten M Boughan, Scott E. Smith, Brad M. Haverkos, Victor M. Orellana-Noia, Vaishalee P. Kenkre, Adam Zayac, Seth M Maliske, Narendranath Epperla, Parameswaran Venugopal, Tatyana A. Feldman, Stephen D. Smith, Andrzej Stadnik, Izidore S. Lossos, Kevin A. David, Seema Naik, Paolo Caimi, Manali Kamdar, Craig A. Portell, Adam J Olszewski, Juan Pablo Alderuccio
Journal: Blood (2019)
Incidence, Natural History and Outcomes of Transient and Persistent Antiphospholipid Antibodies in Children and Young Adults with Provoked Venous Thromboembolism: Analysis of the Kids-DOTT Trial
Authors: Marisol Betensky, Anh Thy Nguyen, Cristina Tarango, Anupam R Verma, Rukhmi Bhat, Nicole Kucine, Charles Nakar, Gary Woods, Frances L Hamblin, Ernest Amankwah, Neil A Goldenberg
Journal: Blood (2019)
Inaugural Readmission Penalties for Total Hip and Total Knee Arthroplasty Procedures Under the Hospital Readmissions Reduction Program
Authors: Benjamin Y. Li, Kenneth L. Urish, Bruce L. Jacobs, Chang He, Tudor Borza, Yongmei Qin, Hye Sung Min, James M. Dupree, Chad Ellimoottil, Brent K. Hollenbeck, Mariel S. Lavieri, Jonathan E. Helm, Ted A. Skolarus
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The Hospital Readmissions Reduction Program (HRRP) is a Centers for Medicare and Medicaid Services policy that levies hospital reimbursement penalties based on excess readmissions of patients with 4 medical conditions and 3 surgical procedures. A greater understanding of factors associated with the 3 surgical reimbursement penalties is needed for clinicians in surgical practice. <h3>Objective</h3> To investigate the first year of HRRP readmission penalties applied to 2 surgical procedures—elective total hip arthroplasty (THA) and total knee arthroplasty (TKA)—in the context of hospital and patient characteristics. <h3>Design, Setting, and Participants</h3> Fiscal year 2015 HRRP penalization data from Hospital Compare were linked with the American Hospital Association Annual Survey and with the Healthcare Cost and Utilization Project State Inpatient Database for hospitals in the state of Florida. By using a case-control framework, those hospitals were separated based on HRRP penalty severity, as measured with the HRRP THA and TKA excess readmission ratio, and compared according to orthopedic volume as well as hospital-level and patient-level characteristics. The first year of HRRP readmission penalties applied to surgery in Florida Medicare subsection (d) hospitals was examined, identifying 60 663 Medicare patients who underwent elective THA or TKA in 143 Florida hospitals. The data analysis was conducted from February 2016 to January 2017. <h3>Exposures</h3> Annual hospital THA and TKA volume, other hospital-level characteristics, and patient factors used in HRRP risk adjustment. <h3>Main Outcomes and Measures</h3> The HRRP penalties with HRRP excess readmission ratios were measured, and their association with annual THA and TKA volume, a common measure of surgical quality, was evaluated. The HRRP penalties for surgical care according to hospital and readmitted patient characteristics were then examined. <h3>Results</h3> Among 143 Florida hospitals, 2991 of 60 663 Medicare patients (4.9%) who underwent THA or TKA were readmitted within 30 days. Annual hospital arthroplasty volume seemed to follow an inverse association with both unadjusted readmission rates (<i>r</i> = −0.16,<i>P</i> = .06) and HRRP risk-adjusted readmission penalties (<i>r</i> = −0.12,<i>P</i> = .14), but these associations were not statistically significant. Other hospital characteristics and readmitted patient characteristics were similar across HRRP orthopedic penalty severity. <h3>Conclusions and Relevance</h3> This study's findings suggest that higher-volume hospitals had less severe, but not significantly different, rates of readmission and HRRP penalties, without systematic differences across readmitted patients.
Building effective quality improvement: start with joy in work
Authors: Rachel Pilling, Dan Wadsworth
Journal: BMJ (2019)

For quality improvement (QI) to have the impact at the pace and scale required, we cannot solely rely on formal programmes, disseminated from the top down.1 We need to mobilise informal power in organisations to help staff to create their own short change cycles.

QI has three main elements; patient safety, cost effectiveness, and joy in work.2 The beauty …
Brentuximab Vedotin and Nivolumab for Relapsed or Refractory Classic Hodgkin Lymphoma: Long-Term Follow-up Results from the Single-Arm Phase 1/2 Study
Authors: Alison J. Moskowitz, Ranjana H Advani, Nancy L. Bartlett, Julie M Vose, Radhakrishnan Ramchandren, Tatyana A. Feldman, Ann S. LaCasce, Beth A. Christian, Stephen M Ansell, Craig H. Moskowitz, Lisa Brown, David Taft, Sahar Ansari, Daniel E. Zak, Mariana Sacchi, Thomas Manley, Alex F. Herrera
Journal: Blood (2019)
Genomic analysis of malaysian breast cancers unravel molecular differences from Caucasian breast cancers
Authors: S.-H. Teo, M. Zabidi, J.W. Pan, P.S. Ng, M.Y. Meng, N. Hasan, B. Sandey, C.H. Yip, P. Rajadurai, O. Rueda, C. Caldas, S.F. Chin
Journal: Annals of Oncology (2019)
Is information theory, or the assumptions that surround it, holding back neuroscience?
Authors: Lee de-Wit, Vebjørn Ekroll, Dietrich Samuel Schwarzkopf, Johan Wagemans
Journal: Behavioral and Brain Sciences (2019)

Abstract The challenges raised in this article are not with information theory per se, but the assumptions surrounding it. Neuroscience isn't sufficiently critical about the appropriate ‘receiver’ or ‘channel’, focuses on decoding ‘parts’, and often relies on a flawed ‘veridicality’ assumption. If these problematic assumptions were questioned, information theory could be better directed to help us understand how the brain works.
Abstract 387: Awareness and Cognitive Activity During Cardiac Arrest
Authors: Sam Parnia, Tara Keshavarz, Meghan McMullin, Tori Williams
Journal: Circulation (2019)

Background: While 50% of cardiac arrest (CA) survivors report negative psychological outcomes including post-traumatic stress disorder (PTSD), depression, and anxiety, 10% report a positive transformational outcome associated with recall of cognitive activity and 2-3% report external awareness during CPR. Though, often referred to using the poorly defined term of near-death experiences (NDE), this aspect of CA survivorship remains ill understood. Methods: In an ongoing prospective study (AWARE-II) we piloted methods to administer audiovisual stimuli to test implicit and explicit memories using a tablet computer with images and sounds delivered during on-going CPR. Results: Among 465 in-hospital CA lasting &gt;5 min, 44 (9%) survived and 21 were interviewed. Of these, 4 (19%) reported explicit memories, including (internal) cognitive processes such as feeling peace, joy, and a perception of seeing relatives, while other memories were suggestive of (external) awareness e.g. hearing people talking, drugs given. One of 19 correctly recalled the audio stimuli given during CPR, but none identified the visual test. In this limited sample, there were no signs of implicit learning. We then compared these to 22 self-reported memories from a registry of CA survivors, Additional themes emerged as follows: 1) a sense of joy and peace (95%), perception of a light (86%), a tunnel (59%), a review and judgment of major life events including a person’s own actions and intentions (54%), and an overall feeling of positive transformation after the event (95%). Conclusion: External awareness and internal cognitive activity may occur during CA. However, it is unclear whether explicit recall sufficiently describes the entirety of cognitive processes during CA, or whether implicit memories may also form. In some survivors, memories lead to greater life-meaning and a positive transformation, which contrasts with negative psychological outcomes such as PTSD. In this context, in place of NDE a more appropriate term might be transformative experience of death (TED). Further studies, are needed to delineate the role of implicit and explicit learning and how cognitive activity during CPR may relate to brain resuscitation quality and overall psychological outcomes.