tbuckley/cabot-search huggingface dataset:
Peptidoglycan inhibits beigeing of adipose tissue
Authors: Hong Chen, Lijun Sun, Lu Feng, Michael Mulholland, Weizhen Zhang, Yue Yin
Journal: Acta Pharmaceutica Sinica B (2021)

Abstract   Obesity, an epidemic metabolic disease characterized by excessive fat accumulation, causes a significant economic burden on families and the society. The discovery of beige adipocytes has provided us with a brand new approach for the intervention of obesity 1 . Beige adipocytes increase energy expenditure and improve the balance of glucose and lipid metabolism. Reduction of beige adipocytes is a hallmark of obesity. Mechanism underlying the decrement of beigeing remains largely unknown.  Intestinal microflora is strongly associated with white adipose tissue beigeing. Removal of intestinal microflora with antibiotic treatment or germ-free mice can effectively promote beigeing of subcutaneous and visceral adipose tissue 2 . However, it is still unclear how the intestinal microflora influences white adipose tissue beigeing. Previous studies have suggested that bacterial products may affect the thermogenesis of white and brown adipose tissue 3 . For example, lipopolysaccharides (LPS) from Gram-negative bacteria have been reported to suppress adaptive thermogenesis 4 . However, studies have shown an increase in the ratio of Gram-positive firmicutes to Gram-negative bacteroidetes 5 . These observations suggest that products of intestinal Gram-positive bacterial may also contribute to modulation of beigeing.  Peptidoglycan (PGN) is a unique and essential structural element in the cell wall of Gram-positive bacteria. It is embedded in a relatively thick cell wall with other polymers, such as lipoteichoic acids (LTAs). Our previous study suggests that PGN plays an important role in insulin resistance and metabolic inflammation 6 . Whether PGN affects the beigeing of adipose tissue remains unclear. PGNs from diverse bacteria function through Toll-like receptor (TLR) 2 to activate multiple signaling such as NFκB and JNK. As a critical molecule in innate immune response 7 , TLR2 may be involved in diet-induced metabolic syndrome. TLR2 deficiency improves insulin sensitivity, beta cell dysfunction and hepatic insulin signaling in mice 8 . It remains unclear whether the beneficial effects of TLR2 deficiency occur indirectly by suppressing inflammatory cells in metabolic tissues or directly by acting on parenchymal cells.  Here we reported that PGN suppresses the white adipose tissue beigeing. This occurs through induction of inflammation in adipose tissue by promoting macrophage M1 polarization. In addition, PGN directly activates TLR2 receptor on adipocytes to suppress beigeing. Intervention of PGN-TLR2 signaling may thus provide a potential strategy for treatment of obesity.
Recognizing Unmet Need in the Era of Targeted Therapy for CLL/SLL: “What's Past Is Prologue” (Shakespeare)
Authors: Anthony R. Mato, Matthew S. Davids, Jeff Sharman, Lindsey E. Roeker, Neil Kay, Arnon P. Kater, Kerry Rogers, Meghan C. Thompson, Joanna Rhodes, Andre Goy, Alan Skarbnik, Stephen J. Schuster, Constantine S. Tam, Toby A. Eyre, Susan O'Brien, Chadi Nabhan, Nicole Lamanna, Clare Sun, Mazyar Shadman, John M. Pagel, Chaitra Ujjani, Danielle Brander, Catherine C. Coombs, Nitin Jain, Chan Y. Cheah, Jennifer R. Brown, John F. Seymour, Jennifer A. Woyach
Journal: Clinical Cancer Research (2021)

Abstract The management of chronic lymphocytic leukemia (CLL) has undergone unprecedented changes over the last decade. Modern targeted therapies are incorporated into clinical practice. Unfortunately, patients have begun to develop resistance or intolerance to multiple classes. Symptomatic patients previously treated with a BTK inhibitor (BTKi) and venetoclax represent a new and rapidly growing unmet need in CLL. Here, we define unmet needs in a modern treatment context. We also critically review the literature for PI3K inhibitors and chemoimmunotherapy and lack of data to support their utility following BTKis and venetoclax. Finally, we suggest opportunities to ensure the continued innovation for patients with CLL.
Drug-Pricing Debate Redux — Should Cost-Effectiveness Analysis Be Used Now to Price Pharmaceuticals?
Authors: Peter J. Neumann, Joshua T. Cohen, Daniel A. Ollendorf
Journal: New England Journal of Medicine (2021)

The idea of permitting the government to negotiate pharmaceutical prices raises a question about the basis for negotiations: how to judge what's a fair price. Absent well-functioning markets, cost-effectiveness analyses can clarify the value that therapies deliver.
AML Cell Vaccines Co-Expressing CD80 and IL-15/IL-15 Receptor Alpha Induce Activation and Cytolytic Activity in Post Remission Autologous Patient PBMC <i>Ex Vivo</i>
Authors: Xinyue Wang, Jeffrey P. Fung, Giulia Parisi, Francesca M. Olguin, Nathaniel Z. Rothschild, Kenneth I. Weinberg, William J. Murphy, Donald B. Kohn, Karin L. Gaensler
Journal: Blood (2021)
Radiomic Phenotypes of High and Low Lesion SUV Components for the Prediction of Refractory Disease in Hodgkin's Lymphoma Patients Treated with ABVD Based Therapy
Authors: Serageldin Kamel, Li-Wei Chen, Gregory Ravizzini, Ho-Feng Chen, Joo Schmidt, Sairah Ahmed, Ranjit Nair, Raphael E Steiner, Branko Cuglievan, Yago Nieto, Roberto N. Miranda, Penny Fang, Jillian R. Gunther, Chelsea C. Pinnix, Michael Wang, Tinsu Pan, Hun Ju Lee
Journal: Blood (2021)
Prospective Comparison Study of Prognostic Value of MRD Detected By 8-Color MFC (EuroFlow-NGF) and NGS in Patients with Multiple Myeloma in ASCT Setting
Authors: Takeshi Yoroidaka, Hiroyuki Takamatsu, Mitsuhiro Itagaki, Satoshi Yoshihara, Kota Sato, Naoki Takezako, Shuji Ozaki, Kazuhito Suzuki, Kentaro Kohno, Morio Matsumoto, Yasushi Terasaki, Takeshi Yamashita, Shin-ichi Fuchida, Ryota Urushihara, Yuji Hiragori, Kenshi Suzuki, Hirokazu Murakami, Shinji Nakao, Brian G.M. Durie, Kazuyuki Shimizu
Journal: Blood (2021)
SEL24/MEN1703 Inhibits PIM/FLT3 Downstream Target in Acute Myeloid Leukemia (AML) Patients: Results of the Pharmacodynamics (PD) Assay and Genomic Profiling in the First-in-Human Diamond-01 Trial
Authors: Alessandro Paoli, Daniela Bellarosa, Alessandro Bressan, Francesco Bertolini, Scott R. Solomon, Pau Montesinos, Sudipto Mukherjee, Stephen A Strickland, Giovanni Marconi, Armando Santoro, Roland B. Walter, Rachel J. Cook, Maria Calbacho, Susana Vives, Salman Fazal, Farhad Ravandi, Krzysztof Brzozka, Tomasz Rzymski, Milena Mazan, Simone Baldini, Niccolò Ravenni, Monica Binaschi, Dirk Laurent, Andrea Pellacani
Journal: Blood (2021)
Interim Analysis of an Open-Label, Ascending-Dose, Phase 1 Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Doses of the Subcutaneously Administered Human Monoclonal Antibody Pozelimab in Combination with Single Doses of the Subcutaneously Administered siRNA Cemdisiran in Healthy Volunteers
Authors: Tavé van Zyl, Jonathan Weyne, Umesh Chaudhari, Olivier Harari, Oren Levy, Jutta Miller, Yiziying Chen, Karoline A Meagher, Merideth L Rodgers, Lorah Perlee, Lori Morton, David M Weinreich, George D. Yancopoulos
Journal: Blood (2021)
Significant Plasma Cell Loss (up to 90%) Despite Preserved Overall Cell Viability - Time Dependent Changes Observed in Multiparametric Flow Cytometry Analysis of Bone Marrow Samples in Multiple Myeloma
Authors: Tukten Rolfe, Quirine O'Loughlin, Heather Campbell, Jordan Barr, Fiona Shawyer, Teng Fong Ng
Journal: Blood (2021)
Abstract 9570: Prognostic Value of Stroke Volume Index in Patients With Pulmonary Arterial Hypertension at Intermediate Risk
Authors: Fabio Dardi, Massimiliano Palazzini, Enrico Gotti, Elisa Zuffa, Alessandro De Lorenzis, Filippo Pasca, Daniele Guarino, Ilenia Magnani, Mariangela Rotunno, Andrea Rinaldi, Alessandra Manes, Nazzareno Galie
Journal: Circulation (2019)

Introduction: current guidelines stratify the risk of pulmonary arterial hypertension (PAH) patients with a multiparametric approach. This risk assessment and a simplified risk table have been rece...
Trends and the course of liver cirrhosis and its complications in Germany: Nationwide population-based study (2005 to 2018)
Authors: Wenyi Gu, Hannah Hortlik, Hans-Peter Erasmus, Louisa Schaaf, Yasmin Zeleke, Frank E. Uschner, Philip Ferstl, Martin Schulz, Kai-Henrik Peiffer, Alexander Queck, Tilman Sauerbruch, Maximilian Joseph Brol, Gernot Rohde, Cristina Sanchez, Richard Moreau, Vicente Arroyo, Stefan Zeuzem, Christoph Welsch, Jonel Trebicka
Journal: The Lancet Regional Health - Europe (2021)

Cirrhosis is known to have a high prevalence and mortality worldwide. However, in Europe, the epidemiology of cirrhosis is possibly undergoing demographic changes, and etiologies may have changed due to improvements in standard of care. The aim of this population-based study was to analyze the trends and the course of liver cirrhosis and its complications in recent years in Germany.
322 Melanoma-intrinsic hypoxia-inducible factor-1α results in diminished T cell accumulation within the tumor microenvironment
Authors: Emily Higgs, Thomas Gajewski, Jonathan Trujillo
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The hypoxia-inducible factor (HIF) system, consisting of the transcription factors HIF-1α and HIF-2α, mediates cellular adaptation to hypoxia, and can promote cancer progression, invasion, and metastasis. HIF pathway activation in the tumor microenvironment has been implicated in cancer immune evasion; however, a direct causal role for tumor cell-intrinsic HIF-1α and HIF-2α activation in mediating T cell exclusion and cancer cell resistance to immune checkpoint inhibitor therapy has not been demonstrated. Methods We performed gene expression analysis of melanoma tumors in the Cancer Genome Atlas (TCGA) data set to determine whether increased HIF-1α pathway activation correlated with reduced T cell-based inflammation. The magnitude of HIF-1α pathway activation across melanoma samples was determined by applying a quantitative scoring system on the expression of a melanocyte-specific hypoxia-induced, HIF-1α-target gene signature consisting of 81 genes. The Pearson correlation test was used to compare the HIF-1α activation score and our 160-gene T-cell-inflamed gene signature. To determine the impact of cancer cell-intrinsic HIF-1α or HIF-2α activation on the endogenous anti-tumor T cell response, we developed an inducible autochthonous mouse melanoma model driven by BRAFV600E expression and PTEN-deletion, with or without inducible expression of either a stabilized variant of HIF-1α or HIF-2α. These murine tumor models are being used to determine the impact of cancer cell-intrinsic HIF-1α or HIF-2α activation on tumor sensitivity to anti-PD-1/PD-L1 and anti-CTLA-4 treatment. Results Gene expression analysis of human melanomas in the TCGA demonstrated a statistically significant inverse correlation between the HIF-1α activation score and T cell-inflammation score. Braf/PTEN murine melanomas with and without stabilized HIF-1α expression developed with comparable tumor onset and growth kinetics. Multiparameter immunofluorescence staining of melanoma tissue revealed a significant decrease in tumor-infiltrating T cells within Braf/PTEN melanoma tumors expressing stabilized HIF-1α compared to control Braf/PTEN melanomas. Conclusions Our data demonstrate that tumor-cell intrinsic HIF-1α activation leads to diminished T cell accumulation within the tumor microenvironment, which has implications for cancer immunotherapy. The mechanism of this effect is being elucidated. These novel murine models will help elucidate the roles of cancer cell-intrinsic HIF-1α and HIF-2α activation in modulating the anti-tumor T cell response, providing mechanistic insight that will inform the evaluation of novel selective HIF inhibitors, which are showing promising anti-tumor activity in clinical trials in patients with advanced solid tumors.
Outcomes of Aggressive B Cell Lymphoma Patients with No Evidence of Measurable Disease at the Time of CD19 Chimeric Antigen Receptor T Cell Therapy: The Experience from the CAR T Cell Consortium
Authors: Kitsada Wudhikarn, Ana Alarcon Tomas, Jamie Brower, Veronika Bachanova, Richard T. Maziarz, Joseph P. McGuirk, Loretta Nastoupil, David L. Porter, Peter A. Riedell, Miguel-Angel Perales
Journal: Blood (2021)
Small area variations and factors associated with blood pressure and body-mass index in adult women in Accra, Ghana: Bayesian spatial analysis of a representative population survey and census data
Authors: Sierra N. Clark, James E. Bennett, Raphael E. Arku, Allan G. Hill, Günther Fink, Richard M. Adanu, Richard B. Biritwum, Rudolph Darko, Ayaga Bawah, Rosemary B. Duda, Majid Ezzati
Journal: PLoS Medicine (2021)

Background Body-mass index (BMI) and blood pressure (BP) levels are rising in sub-Saharan African cities, particularly among women. However, there is very limited information on how much they vary within cities, which could inform targeted and equitable health policies. Our study aimed to analyse spatial variations in BMI and BP for adult women at the small area level in the city of Accra, Ghana. Methods and findings We combined a representative survey of adult women’s health in Accra, Ghana (2008 to 2009) with a 10% random sample of the national census (2010). We applied a hierarchical model with a spatial term to estimate the associations of BMI and systolic blood pressure (SBP) and diastolic blood pressure (DBP) with demographic, socioeconomic, behavioural, and environmental factors. We then used the model to estimate BMI and BP for all women in the census in Accra and calculated mean BMI, SBP, and DBP for each enumeration area (EA). BMI and/or BP were positively associated with age, ethnicity (Ga), being currently married, and religion (Muslim) as their 95% credible intervals (95% CrIs) did not include zero, while BP was also negatively associated with literacy and physical activity. BMI and BP had opposite associations with socioeconomic status (SES) and alcohol consumption. In 2010, 26% of women aged 18 and older had obesity (BMI ≥ 30 kg/m 2 ), and 21% had uncontrolled hypertension (SBP ≥ 140 and/or DBP ≥ 90 mm Hg). The differences in mean BMI and BP between EAs at the 10th and 90th percentiles were 2.7 kg/m 2 (BMI) and in BP 7.9 mm Hg (SBP) and 4.8 mm Hg (DBP). BMI was generally higher in the more affluent eastern parts of Accra, and BP was higher in the western part of the city. A limitation of our study was that the 2010 census dataset used for predicting small area variations is potentially outdated; the results should be updated when the next census data are available, to the contemporary population, and changes over time should be evaluated. Conclusions We observed that variation of BMI and BP across neighbourhoods within Accra was almost as large as variation across countries among women globally. Localised measures are needed to address this unequal public health challenge in Accra.
Incidence of Mental Health Events and Its Association with Survival Among Patients with Diffuse Large B-Cell Lymphoma: A Population-Based Cohort Study
Authors: Inna Gong, Matthew Cheung, Kelvin Chan, Sumedha Arya, Neil Faught, Ning Liu, Oreofe O. Odejide, Gregory A. Abel, Michael Raphael, Anca Prica, Christopher Booth, Thomas M. Kuczmarski, Lee Mozessohn
Journal: Blood (2021)
Abstract 11078: Neighborhood Social Vulnerability is Associated with Major Adverse Cardiovascular Events and Deaths Among Patients Hospitalized with Covid-19: An Analysis of the Aha Covid-19 Cardiovascular Disease Registry
Authors: Shabatun Islam, Gargya Malla, Wei Tian, Yang Song, Dhruv S Kazi, Aditi Nayak, Anurag Mehta, Yi-An Ko, Arshed A Quyyumi, Robert W Yeh, Abhinav Goyal, Rishi Wadhera
Journal: Circulation (2021)

Introduction: The COVID-19 pandemic has disproportionately affected low-income and racial/ethnic minority populations in the US. However, it remains unclear whether hospitalized COVID-19 patients who live in socially vulnerable neighborhoods are more likely to experience major adverse cardiovascular events and/or death. We evaluated the association between neighborhood social vulnerability and in-hospital outcomes in a national cohort of hospitalized COVID-19 patients. Hypothesis: Among patients hospitalized with COVID-19, residence in socially vulnerable neighborhoods is associated with worse in-hospital outcomes. Methods: The American Heart Association COVID-19 Cardiovascular Disease Registry includes patients hospitalized with COVID-19 across 107 hospitals in the US between January 14, 2020 to November 30, 2020. The Social Vulnerability Index (SVI), a composite measure of community vulnerability developed by Center for Disease Control was used to classify the social vulnerability of patients’ place of residence defined by zip codes. We fit multivariable logistic regression models to evaluate the association between patient’s SVI and in-hospital death or major adverse cardiovascular events (MACE, defined as composite of all-cause death, MI, stroke, new onset heart failure, or cardiogenic shock). Results: Among 20,925 hospitalized COVID-19 patients in the registry, 6083 (29.1%) resided in the most vulnerable communities (highest national quartile of SVI). Compared with those in lowest quartile of SVI, patients in the highest quartile were younger (mean age 59.8±17.7 versus 62.0±17.9), more likely to be women (47.1% vs. 43.2%), Black patients (36.1% vs. 13.3%), and less likely to have private insurance (29.0% vs. 39.1%). After adjusting for demographics (age, sex, race/ethnicity), insurance status, and comorbidities, the highest quartile of SVI (compared to lowest) was associated with higher likelihood of in-hospital MACE (OR [95% CI] 1.28 [1.12, 1.46], p&lt;0.001) as well as in-hospital death (OR 1.37 [1.21, 1.54], p&lt;0.001). Conclusion: Hospitalized patients with COVID-19 who reside in more socially vulnerable neighborhoods experience higher rates of in-hospital MACE and death, independent of race and ethnicity.
Abstract 9187: Risk Factors for the Onset of Coronary Artery Calcium in Younger versus Older Persons
Authors: Alexander C Razavi, Norrina B Allen, Omar Dzaye, Erin Michos, Matthew J Budoff, Joao A Lima, James M Shikany, Kiang Liu, Wendy Post, Roger S Blumenthal, Michael J Blaha, Jeffrey Carr, Seamus P Whelton
Journal: Circulation (2021)

Introduction: Modifiable traditional atherosclerotic cardiovascular disease (ASCVD) risk factors (RFs) have a decreased predictive strength with higher ages. Whether the strength of relationship between these RFs and incident coronary artery calcium (CAC) changes with age is unknown. Hypothesis: Modifiable traditional ASCVD RFs will have a weaker association with incident CAC in older versus young adults. Methods: There were 5108 CARDIA and MESA participants without clinical ASCVD and baseline CAC=0. Repeat CAC scoring occurred 10 years later in CARDIA and 3-11 years later in MESA. Multivariable Cox proportional hazards regression calculated hazard ratios and C-statistics for RFs with incident CAC in young (32-45 years), middle-aged (46-64 years) and older adults (65-84 years). Results: A total of 61% of adults were women and 37% were African American. The proportion with incident CAC increased from young (22%) to middle-aged (33%) and older adults (45%). All modifiable traditional RFs were significantly associated with incident CAC except for diastolic blood pressure and HDL-C in young adults, whereas among older adults only a total cholesterol/HDL-C &gt; 3.5 (p=0.04) was significantly associated with incident CAC. Systolic blood pressure was the modifiable RF with the strongest association per 1 standard deviation change for incident CAC in young adults (HR=1.29, 95% CI: 1.13-1.48), conferring lower risks in middle-aged (HR=1.20, 95% CI: 1.06-1.36) and older adults (HR=1.10, 95% CI: 0.96-1.27). Modifiable traditional RFs provided a greater improvement in the C-statistic for incident CAC prediction in young versus middle-aged and older adults ( Table ). Conclusion: Modifiable traditional ASCVD RFs were stronger predictors of incident CAC for young compared to older adults, which may be due to their higher prevalence with increasing age. Further research is needed to examine whether nontraditional RFs improve incident CAC prediction in adults &gt; 65 years old.
Clonal Hematopoiesis Is Frequent and Associated with Inferior Survival Irrespective of Transplantation Strategy in Patients with Newly Diagnosed Multiple Myeloma
Authors: Adam S. Sperling, Robert Redd, Christopher J. Gibson, Peter G. Miller, Jill Corre, Philippe Moreau, Donna S. Neuberg, Mehmet K. Samur, Benjamin L. Ebert, Herve Avet-Loiseau, Nikhil C. Munshi
Journal: Blood (2021)
Real-World Evidence of Brexucabtagene Autoleucel for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
Authors: Gloria Iacoboni, Kai Rejeski, Lina Camacho, Annalisa Chiappella, Serafina Guadagnuolo, Lucía López Corral, Mariana Bastos-Oreiro, Javier Delgado Serrano, Christian Schmidt, Cecilia Carpio, Juan Luis Reguera, Mi Kwon, Alejandro Martín García-Sancho, Pier Luigi Zinzani, Paolo Corradini, Marion Subklewe, Pere Barba
Journal: Blood (2021)
Safety and Efficacy of CD37-Targeting Naratuximab Emtansine PLUS Rituximab in Diffuse Large B-Cell Lymphoma and Other NON-Hodgkin'S B-Cell Lymphomas - a Phase 2 Study
Authors: Moshe Y. Levy, Deepa Jagadeesh, Zhanet Grudeva-Popova, Marek Trněný, Wojciech Jurczak, Halyna Pylypenko, Marc André, Sunita Dwivedy Nasta, Dalit Rechavi-Robinson, Sara Toffanin, Sandrine Micallef, Antoine Attinger, Elisabeth Rouits, Marie-Claude Roubaudi-Fraschini, Panos Orfanos, Mariola Dymkowska, Heidi Nauwelaerts, Sherida Woei-a-Jin
Journal: Blood (2021)
Genomics of Hyperleukocytic Acute Myeloid Leukemia
Authors: Laetitia Largeaud, Sarah Bertoli, Emilie Berard, Suzanne Tavitian, Muriel Picard, Stephanie Dufrechou, Naïs Prade, Francois Vergez, Jean-Baptiste Rieu, Isabelle Luquet, Audrey Sarry, Francoise Huguet, Jean Ruiz, Veronique De Mas, Eric Delabesse, Christian Recher
Journal: Blood (2021)
Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor Natural Killer Cell Therapy in Acute Myeloid Leukemia
Authors: Thao T. Tang, Lindsey F Call, Sommer Castro, Cynthia Nourigat-Mckay, LaKeisha Perkins, Laura Pardo, Amanda R. Leonti, Soheil Meshinchi, Quy Le
Journal: Blood (2021)
Outcomes with Mismatched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation Following Reduced Intensity Conditioning: A Systematic Review and Meta-Analysis
Authors: Moazzam Shahzad, Sibgha Gull Chaudhary, Ezza Tariq, Naira Fatima, Muhammad Arslan, Muhammad Usman Zafar, Amna Y Shah, Mamoon Ahmed, Iqra Anwar, Nausheen Ahmed, Leyla Shune, Ramesh Balusu, Peiman Hematti, Joseph P. McGuirk, Muhammad Umair Mushtaq
Journal: Blood (2021)
Taking over the Territory: A Case of Superdominant Right Coronary Artery
Authors: Abhishek Thandra, Raahat Bansal, Tarun Tandon, Ann Narmi
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Coronary artery anomalies are a diverse group of congenital disorders, with a reported incidence of 0.6 – 1.3%. Congenital absence of the LCX is an extremely rare anomaly, with a frequency of only 0.003% in all patients who undergo coronary angiography. Here, we present a case of 76-year-old female who had an episode of chest pain while she was hospitalized for management of small bowel obstruction with elevated troponin and coronary angiogram showed super-dominant right coronary artery without any obstructive disease.