tbuckley/cabot-search huggingface dataset:
Ex vivo mass cytometry analysis reveals a profound myeloid proinflammatory signature in psoriatic arthritis synovial fluid
Authors: Nicole Yager, Suzanne Cole, Alicia Lledo Lara, Ash Maroof, Frank Penkava, Julian C Knight, Paul Bowness, Hussein Al-Mossawi
Journal: Annals of the Rheumatic Diseases (2021)

Objectives A number of immune populations have been implicated in psoriatic arthritis (PsA) pathogenesis. This study used mass cytometry (CyTOF) combined with transcriptomic analysis to generate a high-dimensional dataset of matched PsA synovial fluid (SF) and blood leucocytes, with the aim of identifying cytokine production ex vivo in unstimulated lymphoid and myeloid cells. Methods Fresh SF and paired blood were either fixed or incubated with protein transport inhibitors for 6 hours. Samples were stained with two CyTOF panels: a phenotyping panel and an intracellular panel, including antibodies to both T cell and myeloid cell secreted proteins. Transcriptomic analysis by gene array of key expanded cell populations, single-cell RNA-seq, ELISA and LEGENDplex analysis of PsA SF were also performed. Results We observed marked changes in the myeloid compartment of PsA SF relative to blood, with expansion of intermediate monocytes, macrophages and dendritic cell populations. Classical monocytes, intermediate monocytes and macrophages spontaneously produced significant levels of the proinflammatory mediators osteopontin and CCL2 in the absence of any in vitro stimulation. By contrast minimal spontaneous cytokine production by T cells was detected. Gene expression analysis showed the genes for osteopontin and CCL2 to be among those most highly upregulated by PsA monocytes/macrophages in SF; and both proteins were elevated in PsA SF. Conclusions Using multiomic analyses, we have generated a comprehensive cellular map of PsA SF and blood to reveal key expanded myeloid proinflammatory modules in PsA of potential pathogenic and therapeutic importance.
Abstract IA011: Conventional dendritic cells as regulators of therapeutic response in pancreas cancer
Authors: David G. DeNardo
Journal: Cancer Research (2021)

Abstract In these studies, we utilized spontaneous models of pancreatic and lung cancer to examine how neo-antigenicity shapes tumor immunity and progression. As expected, neoantigen expression during lung adenocarcinoma development leads to T cell-mediated immunity and disease restraint. By contrast, neoantigen expression in pancreatic ductal adenocarcinoma (PDAC) resulted in exacerbation of the inflammatory and fibrotic tumor microenvironment that drives disease progression and metastasis. Pathogenic TH17 responses are responsible for this neoantigen-induced tumor progression in PDAC. Underlying these divergent T cell responses in pancreas and lung cancer are differences in infiltrating conventional dendritic cells (cDCs). Overcoming cDC deficiency in early- stage PDAC leads to disease restraint, while restoration of cDC function thru treatment with both CD40 agonists and FLT3L in advanced PDAC restores tumor-restraining immunity and enhances responsiveness to radiation therapy. Citation Format: David G. DeNardo. Conventional dendritic cells as regulators of therapeutic response in pancreas cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA011.
Medical imaging and nuclear medicine: a Lancet Oncology Commission
Authors: Hedvig Hricak, May Abdel-Wahab, Rifat Atun, Miriam Mikhail Lette, Diana Paez, James A Brink, Lluís Donoso-Bach, Guy Frija, Monika Hierath, Ola Holmberg, Pek-Lan Khong, Jason S Lewis, Geraldine McGinty, Wim J G Oyen, Lawrence N Shulman, Zachary J Ward, Andrew M Scott
Journal: The Lancet Oncology (2021)
Abstract 16388: Efficacy and Safety of Early Dalcetrapib Treatment on Lipid Profile and Markers of HDL Functionality in Patients Hospitalized for an Acute Coronary Syndrome - The dal-ACUTE Study
Authors: Kausik Ray, Marc Ditmarsch, David Kallend, Gabriela Suchankova, Judith Anzures-Cabrera, Ruchi Upmanyu, Valerie Lehnert, Meike Pauly-Evers, Eric J Niesor, Ingar M Holme, Josef Stasek, Maarten W van Hessen, Peter H Jones
Journal: Circulation (2012)

Introduction: The dal-ACUTE study assessed the efficacy and safety of the CETP modulator dalcetrapib in patients with a recent acute coronary syndrome (ACS) event. Methods: In this Phase III, multi...
Impact of subsequent therapy on survival in KEYNOTE-361: Pembrolizumab (pembro) plus chemotherapy (chemo) or pembro alone versus chemo as first-line therapy for advanced urothelial carcinoma (UC).
Authors: Ajjai Shivaram Alva, Tibor Csőszi, Mustafa Ozguroglu, Nobuaki Matsubara, Lajos Geczi, Susanna Y. Cheng, Yves Fradet, Stephane Oudard, Christof Vulsteke, Rafael Morales-Barrera, Aude Flechon, Seyda Gunduz, Yohann Loriot, Alejo Rodriguez-Vida, Ronac Mamtani, Evan Y. Yu, Kijoeng Nam, Kentaro Imai, Blanca Homet Moreno, Thomas Powles
Journal: Journal of Clinical Oncology (2021)

439 Background: The phase III KEYNOTE-361 study examined the efficacy and safety of 1L pembro + chemo or pembro alone vs chemo for pts with advanced UC. The PFS and OS benefit of pembro + chemo vs chemo did not reach statistical significance; no further formal tesing was done. We present an exploratory analysis of OS by subsequent therapy in KEYNOTE-361 (NCT02853305) to assess how 1L and 2L therapy selection affected survival outcomes; no formal comparisons were conducted. Methods: OS was estimated for pts by whether they received subsequent therapy, and by whether subsequent therapy included an anti–PD-(L)1 agent. Results: 351 pts were randomized to pembro + chemo, 307 pts to pembro, and 352 pts to chemo. As of Apr 29, 2020, the median (range) time from randomization to data cutoff was 31.7 (22.0-42.3) mo. 124/351 pts (35%) in the pembro + chemo arm, 126/307 pts (41%) in the pembro arm, and 215/352 pts (61%) in the chemo arm received any subsequent therapy. Similar rates of subsequent therapy (pembro + chemo: 32%; pembro: 43%; chemo: 59%) were observed for pts who experienced progressive disease (PD) by blinded independent central review (BICR). A higher rate of pts (169/352 [48%]) in the chemo arm received subsequent anti–PD-(L)1 therapy than in either the pembro + chemo arm (23/351 [7%]) or pembro arm (14/307 [5%]). Due to the small pt numbers, pts in the pembro + chemo or pembro arms who received subsequent anti−PD-(L)1 were not considered further. This analysis included all pts who received 2L therapy (465/1010 pts [46%]); the rate of 2L therapy was similar in pts with PD by BICR (274/615 [45%]). Chemo agents alone or in combination, specifically carboplatin, cisplatin, docetaxel, doxorubicin, gemcitabine, and paclitaxel, were the most commonly received subsequent therapies for pts who did not receive anti–PD-(L)1 in 2L. Pts who received 1L chemo followed by subsequent anti–PD-(L)1 had longer mOS (19.1 mo [95% CI 16.2-22.2]) than pts with 1L pembro followed by 2L therapy not including an anti−PD-(L)1 agent (16.0 mo [95% CI 11.8-19.2]) (Table). Conclusions: In this exploratory analysis, favorable survival outcomes were observed for pts who received 1L chemo followed by anti–PD-(L)1 compared with pts who received 1L pembro followed by 2L therapy not including an anti–PD-(L)1 agent. These data underline the continued importance of immunotherapy as 2L therapy for advanced UC. Clinical trial information: NCT02853305 . Research Sponsor: Merck &amp; Co., Inc[Table: see text]
Abstract 10930: Trans-Radial Percutaneous Coronary Intervention for Patients With Severe Chronic Renal Insufficiency and/or on Dialysis
Authors: Toshiki Kuno, Keita Hirano, Takayuki Abe, Syohei Imaeda, Kenji Hashimoto, Toshinobu Ryuzaki, Souichi Yokokura, Hiroyuki Yamazaki, Ryota Tabei, Masaki Kodaira, Yohei Numasawa
Journal: Circulation (2018)

Introduction: Periprocedural bleeding is associated with increased risk of early mortality during percutaneous coronary intervention (PCI), especially in these patients. TRI should be considered in...
In hyponatremia, rapid intermittent bolus vs. slow continuous infusion of hypertonic saline did not differ for overcorrection of serum sodium
Authors: Anthony A. Donato, Benjamin J. Lloyd
Journal: Annals of Internal Medicine (2021)

Source Citation Baek SH, Jo YH, Ahn S, et al. Risk of overcorrection in rapid intermittent bolus vs slow continuous infusion therapies of hypertonic saline for patients with symptomatic hyponatremia: the SALSA randomized clinical trial. JAMA Intern Med. 2021;181:81-92. 33104189
Mental Health and Chemical Dependency Services at US Cancer Centers
Authors: Shehzad K. Niazi, Aaron Spaulding, Emily Brennan, Sarah K. Meier, Julia E. Crook, Lauren F. Cornell, Sikander Ailawadhi, Matthew M. Clark, Teresa A. Rummans
Journal: Journal of the National Comprehensive Cancer Network (2021)

It is standard of care and an accreditation requirement to screen for and address distress and psychosocial needs in patients with cancer. This study assessed the availability of mental health (MH) and chemical dependency (CD) services at US cancer centers.The 2017-2018 American Hospital Association (AHA) survey, Area Health Resource File, and Centers for Medicare & Medicaid Services Hospital Compare databases were used to assess availability of services and associations with hospital-level and health services area (HSA)-level characteristics.Of 1,144 cancer centers surveyed, 85.4% offered MH services and 45.5% offered CD services; only 44.1% provided both. Factors associated with increased adjusted odds of offering MH services were teaching status (odds ratio [OR], 1.76; 95% CI, 1.18-2.62), being a member of a hospital system (OR, 2.00; 95% CI, 1.31-3.07), and having more beds (OR, 1.04 per 10-bed increase; 95% CI, 1.02-1.05). Higher population estimate (OR, 0.98; 95% CI, 0.97-0.99), higher percentage uninsured (OR, 0.90; 95% CI, 0.86-0.95), and higher Mental Health Professional Shortage Area level in the HSA (OR, 0.99; 95% CI, 0.98-1.00) were associated with decreased odds of offering MH services. Government-run (OR, 2.85; 95% CI, 1.30-6.22) and nonprofit centers (OR, 3.48; 95% CI, 1.78-6.79) showed increased odds of offering CD services compared with for-profit centers. Those that were members of hospital systems (OR, 1.61; 95% CI, 1.14-2.29) and had more beds (OR, 1.02; 95% CI, 1.01-1.03) also showed increased odds of offering these services. A higher percentage of uninsured patients in the HSA (OR, 0.92; 95% CI, 0.88-0.97) was associated with decreased odds of offering CD services.Patients' ability to pay, membership in a hospital system, and organization size may be drivers of decisions to co-locate services within cancer centers. Larger organizations may be better able to financially support offering these services despite poor reimbursement rates. Innovations in specialty payment models highlight opportunities to drive transformation in delivering MH and CD services for high-need patients with cancer.
Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC).
Authors: Dana E. Rathkopf, Eleni Efstathiou, Gerhardt Attard, Thomas W. Flaig, Fabio Andre Franke, Oscar B. Goodman, Stephane Oudard, Thomas Steuber, Hiroyoshi Suzuki, Daphne Wu, Kesav Yeruva, Peter De Porre, Sabine Doris Brookman-May, Susan Li, Jinhui Li, Suneel Mundle, Sharon Anne McCarthy, Fred Saad
Journal: Journal of Clinical Oncology (2021)

9 Background: As mCRPC is driven by activated androgen receptors and elevated intratumoral androgens, androgen annihilation may require dual inhibition. APA and AA are approved prostate cancer therapies that have distinct receptor inhibition and ligand suppression actions, respectively. ACIS compared radiographic progression-free survival (rPFS) of APA + AAP vs PBO + AAP in chemo-naive mCRPC. Methods: mCRPC pts with ongoing androgen deprivation therapy (ADT) but no other life-prolonging treatment since diagnosis were randomized 1:1 to APA (240 mg po QD) + AA (1000 mg po QD) + P (5 mg po BID) or PBO + AAP (stratified by presence or absence of visceral metastases, Eastern Cooperative Oncology Group performance status 0 or 1, and geographic region). The primary end point was rPFS (investigator assessed; defined from randomization date to radiographic progression date or death). Secondary/other end points included prostate-specific antigen (PSA) response, overall survival (OS), safety, time to PSA progression, chronic opioid use, initiation of cytotoxic chemotherapy, and pain progression. Results: 982 pts were enrolled (Dec 2014 to Aug 2016). Median rPFS was extended 6 mos with APA + AAP (22.6 mos) vs AAP (16.6 mos) (HR 0.69 [95% CI 0.58-0.83]; p &lt; 0.0001) at the final analysis for rPFS, coinciding with the first interim analysis of OS (median follow-up time 25.7 mo). At final analysis, treatment with APA + AAP vs AAP showed a significantly higher rate of confirmed ≥ 50% PSA decline. Although not statistically significant, treatment with APA + AAP vs AAP showed a longer median OS. Time to PSA progression, chronic opioid use, initiation of cytotoxic chemotherapy, and pain progression did not differ statistically significantly between arms. The safety profile was consistent with prior drug experience, with no new safety concerns. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 63.3% (310/490) of APA + AAP–treated pts vs 56.2% (275/489) of AAP-treated pts, with more grade 3 (56.1%, 275/490 vs 45.6%, 223/489) and less grade 4 (7.1%, 35/490 vs 10.6%, 52/489) TEAEs, respectively. Results based on biomarker subpopulations and quality of life will be presented. Conclusions: The ACIS final analysis met the primary end point and demonstrated a 31% reduction in risk of radiographic progression or death in chemo-naive mCRPC pts treated with the combination of APA + AAP with ADT vs AAP with ADT. Funding: Janssen Research &amp; Development. Trial registration: NCT02257736. Clinical trial information: NCT02257736. [Table: see text]
Smart wearable devices in cardiovascular care: where we are and how to move forward
Authors: Karim Bayoumy, Mohammed Gaber, Abdallah Elshafeey, Omar Mhaimeed, Elizabeth H. Dineen, Francoise A. Marvel, Seth S. Martin, Evan D. Muse, Mintu P. Turakhia, Khaldoun G. Tarakji, Mohamed B. Elshazly
Journal: Nature Reviews Cardiology (2021)
Abstract 20884: Complement Up-Regulate Runx2 to Induce Pro-Fibrogenic Change in Human Aortic Valve Interstitial Cells (AVICs)
Authors: Xinsheng Deng, Xiangzhong Meng, David Fullerton, James Jaggers
Journal: Circulation (2017)

Introduction: Accumulation of fibrotic tissue and calcium in aortic valves leads to calcific aortic valve disease (CAVD). Complement end products and their receptors are found in human stenotic aor...
Long-term evolution and short-term adaptation of microbiota strains and sub-strains in mice
Authors: Bahtiyar Yilmaz, Catherine Mooser, Irene Keller, Hai Li, Jakob Zimmermann, Lars Bosshard, Tobias Fuhrer, Mercedes Gomez de Agüero, Nerea Fernandez Trigo, Heidi Tschanz-Lischer, Julien P. Limenitakis, Wolf-Dietrich Hardt, Kathy D. McCoy, Bärbel Stecher, Laurent Excoffier, Uwe Sauer, Stephanie C. Ganal-Vonarburg, Andrew J. Macpherson
Journal: Cell Host & Microbe (2021)
Radical prostate radiotherapy and the use of androgen deprivation in the era of risk stratification: Does real-world practice follow the evidence?
Authors: Mark Prentice, Sheila Mpima, Paola Nasuti, Heather Ann Payne
Journal: Journal of Clinical Oncology (2021)

216 Background: Prostate cancer is a common condition with varied pathologies based on stage, grade and presenting PSA allowing non-metastatic cases to be risk stratified at presentation. There is an evidence base for the use of Androgen Deprivation Therapy (ADT) combined with radical radiation showing a survival benefit but with an increase in patient morbidity. Prostate cancer risk stratification can be used to guide ADT therapy duration to reduce toxicity but it is unknown how closely these guidelines are followed internationally. Methods: A cross sectional survey collecting data on 15,255 patients with prostate cancer was conducted across 5 European countries and Japan. Data was interrogated to provide real-world evidence for ADT prescribing in combination with radical radiotherapy treatment and compared against the available evidence base and international best practice guidelines. Results: 3,393 patients were included in data analysis; 53% were high risk, 35% intermediate, and 12% low risk cases. 48% of patients were ages 71-80yrs with 10% being aged over 80. Data, including proposed length of hormone treatment was available for 2,832 patients. Concordance to the evidence base was good for high- and low-risk prostate cancer patients (64% and 96% respectively) but there was more disparity in the intermediate risk group with a concordance rate of only 28%. Conclusions: The data was robust enough to be interrogated and produce meaningful results. Concordance to the evidence base was high in both high and low risk disease although there was a tendency towards over-treatment in both these groups in some of the countries included. There was significant disparity in the intermediate risk group with evidence of both over- and potential under-treatment across all countries. Any potential over treatment with ADT needs to take account of the known evidence base and the potential for bone and metabolic toxicities. The data suggests that guidelines offering greater clarity on the role of ADT in intermediate risk prostate cancer may be beneficial.
Physical Exercise as a Resilience Factor to Mitigate COVID-Related Allostatic Overload
Authors: Ajandek Eöry, Dora Békési, Ajandok Eöry, Sandor Rózsa
Journal: Psychotherapy and Psychosomatics (2021)

The long-lasting threat of COVID-19 makes it necessary to explore strategies to improve coping skills which enable us to master a balanced life in the face of adversity.To unravel the most challenging aspects of COVID-19 in a nonclinical adult population and identify predictors of lost balance and consequent allostatic overload (AO). We examined the role of regular, moderate-intensity formula aerobic exercise (312 meridian exercise) in preventing allostatic overload through increasing well-being.An online survey was conducted to measure CO-VID-related allostatic overload according to clinimetric criteria. The Psychosocial Index (PSI), Kellner's Symptom Questionnaire (KSQ), short Depression Anxiety Stress Scales (DASS-21), Public Health Surveillance Well-Being Scale -(PHS-WB), and Whiteley-7 were used to explore mental health characteristics. Univariate statistics logistic regression analysis and a general linear model were used.According to 442 valid answers, 217 adults practiced physical exercise (PE) frequently (fPE, 3-5 times/every day) while 120 did it less regularly (1-2 times/week), and 105 did not exercise/practiced irregularly (controls). Restriction-related stressors were most challenging, resulting in AO in 29% (n = 128) of the sample. The main predictors were additional stressors (p = 0.005) and anxiety symptoms (p < 0.001). The prevalence of AO was lower (p = 0.018) in the fPE group when compared to controls. KSQ distress symptoms were also lower in fPE (p < 0.0001), while total well-being was increased (p < 0.001) after adjusting for sex, age, and number of chronic diseases. According to the PHS-WB, both physical and mental well-being were higher (p = 0.003 and p = 0.004, respectively) in fPE.Frequent moderate exercise is associated with better mental and physical well-being and a lower prevalence of AO.
Surveillance failure in ultrasound for hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Dong Hwan Kim, Seung Baek Hong, Sang Hyun Choi, So Yeon Kim, Ju Hyun Shim, Ji Sung Lee, Joon-Il Choi, Suk Kim
Journal: Gut (2021)

Recently, various advances have been achieved in the diagnosis and treatment of hepatocellular carcinoma (HCC).1 We read with great interest the paper by De Toni et al 2 demonstrating the importance of early diagnosis of HCC by surveillance with respect to survival benefits, and that by Zeng et al 3 emphasising risk stratifications in HCC surveillance. As these papers suggest, effective surveillance to detect early stage HCC is crucial in the management of patients at-risk.

Although ultrasound (US) is recommended as a standard surveillance modality,4 5 the sensitivity of US for detecting early stage HCC is suboptimal, being only 47%.6 Updated guidelines suggest alternative surveillance tools including MRI in patients likely to have inadequate US examinations.4 5 Recently, MRI surveillance, including abbreviated MRI-protocols, has been drawing attention because of its high diagnostic performance compared with US.7 8 However, considering its cost and availability, MRI surveillance cannot be applied to all at-risk patients, but should be done in patients who are prone to US surveillance failures and benefit from MRI surveillance. Thus, we conducted a meta-analysis to evaluate the incidence …
Recruitment and Results Reporting of COVID-19 Randomized Clinical Trials Registered in the First 100 Days of the Pandemic
Authors: Perrine Janiaud, Cathrine Axfors, John P. A. Ioannidis, Lars G. Hemkens
Journal: JAMA Network Open (2021)

This survey analysis of randomized clinical trials registered within 100 days of the first reported case of coronavirus disease 2019 assessed recruitment and results reporting.
Hepatic Gadd45β promotes hyperglycemia and glucose intolerance through DNA demethylation of PGC-1α
Authors: Ling Wu, Yang Jiao, Yao Li, Jingjing Jiang, Lin Zhao, Menghui Li, Bin Li, Zheng Yan, Xuejin Chen, Xiaoying Li, Yan Lu
Journal: The Journal of Experimental Medicine (2021)

Although widely used for their potent anti-inflammatory and immunosuppressive properties, the prescription of glucocorticoid analogues (e.g., dexamethasone) has been associated with deleterious glucose metabolism, compromising their long-term therapeutic use. However, the molecular mechanism remains poorly understood. In the present study, through transcriptomic and epigenomic analysis of two mouse models, we identified a growth arrest and DNA damage-inducible β (Gadd45β)–dependent pathway that stimulates hepatic glucose production (HGP). Functional studies showed that overexpression of Gadd45β in vivo or in cultured hepatocytes activates gluconeogenesis and increases HGP. In contrast, liver-specific Gadd45β-knockout mice were resistant to high-fat diet– or steroid-induced hyperglycemia. Of pathophysiological significance, hepatic Gadd45β expression is up-regulated in several mouse models of obesity and diabetic patients. Mechanistically, Gadd45β promotes DNA demethylation of PGC-1α promoter in conjunction with TET1, thereby stimulating PGC-1α expression to promote gluconeogenesis and hyperglycemia. Collectively, these findings unveil an epigenomic signature involving Gadd45β/TET1/DNA demethylation in hepatic glucose metabolism, enabling the identification of pathogenic factors in diabetes.
Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis
Authors: Scott R. Goldsmith, Muhammad Bilal Abid, Jeffery J. Auletta, Asad Bashey, Amer Beitinjaneh, Paul Castillo, Roy F. Chemaly, Min Chen, Stefan Ciurea, Christopher E. Dandoy, Miguel Ángel Díaz, Ephraim Fuchs, Siddhartha Ganguly, Christopher G. Kanakry, Jennifer A. Kanakry, Soyoung Kim, Krishna V. Komanduri, Maxwell M. Krem, Hillard M. Lazarus, Hongtao Liu, Per Ljungman, Richard Masiarz, Carolyn Mulroney, Sunita Nathan, Taiga Nishihori, Kristin M. Page, Miguel-Angel Perales, Randy Taplitz, Rizwan Romee, Marcie Riches
Journal: Blood (2021)