tbuckley/cabot-search huggingface dataset:
Abstract PO008: Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort
Authors: Madhura Kulkarni, Pooja M. Vaid, Anirudha Puntambekar Puntambekar, Rituja A. Banale, Ruhi Reddy, Rohini Unde, Namrata Namewar, Devaki Kelkar, L.S. Shashidhara, C.B. Koppiker
Journal: Cancer Research (2021)

Abstract Objectives: Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods: A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&amp;E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results: Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion: Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC. Citation Format: Madhura Kulkarni, Pooja M. Vaid, Anirudha Puntambekar Puntambekar, Rituja A. Banale, Ruhi Reddy, Rohini Unde, Namrata Namewar, Devaki Kelkar, L.S. Shashidhara, C.B. Koppiker. Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort [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 PO008.
Management of fibroblast growth factor receptor inhibitor (FGFRi) treatment-emergent adverse events (TEAEs) of interest in patients (Pts) with locally advanced or metastatic urothelial carcinoma (mUC).
Authors: Arlene O. Siefker-Radtke, Andrea Necchi, Se Hoon Park, Jesús García-Donas, Robert A Huddart, Earle F Burgess, Mark T. Fleming, Arash Rezazadeh, Begona Mellado, Sergei Varlamov, Monika Joshi, Ignacio Duran, Scott T. Tagawa, Yousef Zakharia, Keqin Qi, Manish Monga, Manu Sondhi, Anne OHagan, Yohann Loriot
Journal: Journal of Clinical Oncology (2021)

426 Background: Erdafitinib (ERDA), a pan-FGFR kinase inhibitor, was US FDA approved for adults with mUC with susceptible FGFR3/2 alterations ( FGFRa) who progressed on ≥ 1 line of prior platinum-based chemotherapy based on primary results of the BLC2001 trial (NCT02365597). At final analysis (median 2-y follow-up), ERDA showed median OS of 11.3 mo and a manageable safety profile. Some FGFRi toxicities are distinct from those of other small-molecule TKIs. Proactive AE management can avoid treatment discontinuation, ensuring maximum benefit. We report the frequency and management of TEAEs of interest (central serous retinopathy [CSR], hyperphosphatemia [“on-target” FGFRi class effect], stomatitis, and skin and nail toxicities) for the optimal schedule of ERDA from the final analysis of BLC2001. Methods: The open-label, phase II BLC2001 study enrolled pts with measurable mUC, prespecified FGFRa, and progression during/after ≥ 1 line of prior chemotherapy or ≤ 12 mos of (neo)adjuvant chemotherapy or who were cisplatin ineligible, chemo naive. Optimal dose schedule in the study was 8 mg/d continuous ERDA in 28-d cycles with uptitration to 9 mg/d (ERDA 8 mg/d UpT) if prespecified serum phosphate level was not reached and no significant TEAEs occurred. ERDA 8 mg/d UpT safety results as of Aug 9, 2019 (final analysis) are summarized here. AEs were graded using NCI CTCAE v4.0. Results: Median follow-up for 101 pts treated with ERDA 8 mg/d UpT was 24.0 mos; median treatment duration was 5.4 mos. All pts had ≥ 1 TEAE. Hyperphosphatemia, stomatitis, nail disorders, skin disorders, and CSR TEAEs occurred in 78%, 59%, 59%, 55%, and 27% of pts, respectively (few were grade [gr] 3; none were gr ≥ 4; Table). TEAEs were mostly managed with concomitant treatment and dose modifications. As of data cutoff, hyperphosphatemia had resolved in 74/79 (94%) pts; stomatitis in 44/60 (73%); nail and skin TEAEs in 26/60 (43%) and 25/55 (45%), respectively; and CSR in 17/27 (63%). Most unresolved TEAEs were gr 1–2. No treatment-related deaths occurred. Conclusions: ERDA had measurable benefit in pts with advanced UC with FGFRa. As with other targeted therapies, exposure to ERDA is associated with a pattern of AEs. The most common and FGFRi class effect TEAEs were generally reversible and managed by supportive care and dose modification. Clinical trial information: NCT02365597 . Research Sponsor: Janssen Research &amp; Development, LLC[Table: see text]
Effect of SMS reminders on PrEP adherence in young Kenyan women (MPYA study): a randomised controlled trial
Authors: Jessica E Haberer, Elizabeth A Bukusi, Nelly R Mugo, Maria Pyra, Catherine Kiptinness, Kevin Oware, Lindsey E Garrison, Katherine K Thomas, Nicholas Musinguzi, Susan Morrison, Peter L Anderson, Kenneth Ngure, Jared M Baeten, Jessica E Haberer, Jared M Baeten, Elizabeth A Bukusi, Nelly Mugo, Kenneth Ngure, Ruanne Barnabas, Harsha Thirumurthy, Ingrid Katz, Kevin Oware, Josephine Odoyo, Linda Aswani, Lawrence Juma, Elizabeth Koyo, Bernard Rono, Stanley Cheruiot, Vallery Ogello, Loice Okumu, Violet Kwach, Alfred Obiero, Stella Njuguna, Millicent F Akinyi, Lilian Adipo, Sylvia Akinyi, Catherine Kiptiness, Nicholas Thuo, Stephen G Maina, Irene Njeru, Peter Mogere, Sarah Mbaire, Murugi Micheni, Lynda Oluoch, John Njoroge, Snaidah Ongachi, Jacinta Nyokabi, Lindsey Garrison, Maria Pyra, Katherine K Thomas, Nicholas Musinguzi, Susie Valenzuela, Susan Morrison
Journal: The Lancet HIV (2021)
Urethral recurrence following radical cystectomy: Risk factors and outcomes.
Authors: Abhinav Khanna, Andrew Zganjar, Paras Shah, Matthew K. Tollefson, R. Jeffrey Karnes, Vidit Sharma, Robert F. Tarrell, Prabin Thapa, R. Houston Thompson, Igor Frank, Stephen A. Boorjian
Journal: Journal of Clinical Oncology (2021)

416 Background: Urethral recurrence (UR) has been reported to occur in up to 5% of patients following radical cystectomy (RC). Debate continues regarding the utility of screening for UR after RC. Moreover, oncologic outcomes of patients with UR remain incompletely described, and reports have been limited by small cohort sizes. Herein, we evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. Methods: We reviewed our institutional RC registry to identify patients with UR following RC. Logistic regression was used to assess risk factors for UR. Kaplan-Meier and Cox proportional hazard regression were used to compare outcomes in those with UR diagnosis prompted by symptoms versus those with asymptomatic UR diagnosed on surveillance cytology. Results: Overall, 2930 patients underwent RC from 1980-2018, with a median post-operative follow-up of 4.9 years (IQR 1.6-11.0), of whom 144 (4.9%) were subsequently diagnosed with UR. Prostatic urethral involvement at RC (odds ratio [OR] 5.75 [3.67-9.01], p &lt; 0.0001) and higher pT-stage (OR 3.57 [2.07-6.14], p &lt; 0.0001) were associated with an increased risk of UR, whereas receipt of continent urinary diversion (OR 0.34 [0.20-0.58], p &lt; 0.0001) was associated with a decreased risk of UR. A total of 72/144 (50%) patients were diagnosed with UR based on symptoms, and 104/144 (72.2%) patients with UR underwent subsequent urethrectomy. Patients with symptomatic recurrence had higher tumor stage on urethrectomy than those with asymptomatic recurrence (≥pT2 in 13.1% vs 3.1%, p = 0.007). At a median follow-up of 2.6 years (IQR 1.0-7.1) after UR, 68 of the patients with UR died of urothelial carcinoma. Kaplan-Meier analyses suggest longer median overall and cancer-specific survival for patients with UR detected by cytology than those presenting with symptoms (p = 0.05 for both). On multivariable analyses, patients who experienced UR had significantly increased risk of cancer-specific (hazard ratio [HR] 1.93 [95% confidence interval 1.50-2.50), p &lt; 0.0001) and all-cause mortality (HR 1.34 [1.13-1.65], p = 0.001). Conclusions: Approximately 5% of patient undergoing RC experience UR, with higher pT-stage and prostatic urethral involvement increasing the risk of UR. Asymptomatic detection of UR was associated with lower pathologic stage at urethrectomy as well as longer cancer-specific and overall survival, supporting urethral surveillance after RC.
Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR–T-cell responses against ALL
Authors: Wenting Zheng, Jun Wei, Caitlin C. Zebley, Lindsay L. Jones, Yogesh Dhungana, Yong-Dong Wang, Jayadev Mavuluri, Lingyun Long, Yiping Fan, Ben Youngblood, Hongbo Chi, Terrence L. Geiger
Journal: Blood (2021)
Combinatory Delivery of Etoposide and siCD47 in a Lipid Polymer Hybrid Delays Lung Tumor Growth in an Experimental Melanoma Lung Metastatic Model
Authors: Hend Mohamed Abdel‐Bar, Adam A. Walters, Julie Tzu‐Wen Wang, Khuloud T. Al‐Jamal
Journal: Advanced Healthcare Materials (2021)

Abstract This study investigated the feasibility of lipid polymer hybrid nanoparticles (LPH) as a platform for the combinatorial delivery of small interfering RNA (siRNA) and etoposide (Eto). Different Eto loaded LPH formulations (LPH Eto ) are prepared. The optimized cationic LPH Eto with a particle size of 109.66 ± 5.17 nm and Eto entrapment efficiency (EE %) of 80.33 ± 2.55 is used to incorporate siRNA targeting CD47 (siCD47), a do not eat me marker on the surface of cancer cells. The siRNA‐encapsulating LPH (LPH siNEG‐Eto ) has a particle size of 115.9 ± 4.11 nm and siRNA EE % of 63.54 ± 4.36 %. LPHs improved the cellular uptake of siRNA in a dose‐ and concentration‐dependent manner. Enhanced cytotoxicity (3.8‐fold higher than Eto solution) and high siRNA transfection efficiency (≈50 %) are obtained. An in vivo biodistribution study showed a preferential uptake of the nanosystem into lung, liver, and spleen. In an experimental pseudo‐metastatic B16F10 lung tumor model, a superior therapeutic outcome can be observed in mice treated with combinatory therapy. Immunological studies revealed elevated CD4+, CD8+ cells, and macrophages in the lung following combinatory treatment. The study suggests the potential of the current system for combinatory chemotherapy and immunotherapy for the treatment of lung cancer or lung metastasis.
Preexisting and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs
Authors: Candida Vitale, Chiara Salvetti, Valentina Griggio, Marika Porrazzo, Luana Schiattone, Giulia Zamprogna, Andrea Visentin, Francesco Vassallo, Ramona Cassin, Gian Matteo Rigolin, Roberta Murru, Luca Laurenti, Paolo Rivela, Monia Marchetti, Elsa Pennese, Massimo Gentile, Elia Boccellato, Francesca Perutelli, Maria Chiara Montalbano, Lorenzo De Paoli, Gianluigi Reda, Lorella Orsucci, Livio Trentin, Antonio Cuneo, Alessandra Tedeschi, Lydia Scarfò, Gianluca Gaidano, Francesca Romana Mauro, Robin Foà, Mario Boccadoro, Marta Coscia
Journal: Blood (2021)
Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology
Authors: Seung-Hye Lee, William J. Meilandt, Luke Xie, Vineela D. Gandham, Hai Ngu, Kai H. Barck, Mitchell G. Rezzonico, Jose Imperio, Guita Lalehzadeh, Melanie A. Huntley, Kimberly L. Stark, Oded Foreman, Richard A.D. Carano, Brad A. Friedman, Morgan Sheng, Amy Easton, Christopher J. Bohlen, David V. Hansen
Journal: Neuron (2021)
Risk Factors Associated With SARS-CoV-2 Seropositivity Among US Health Care Personnel
Authors: Jesse T. Jacob, Julia M. Baker, Scott K. Fridkin, Benjamin A. Lopman, James P. Steinberg, Robert H. Christenson, Brent King, Surbhi Leekha, Lyndsay M. O’Hara, Peter Rock, Gregory M. Schrank, Mary K. Hayden, Bala Hota, Michael Y. Lin, Brian D. Stein, Patrizio Caturegli, Aaron M. Milstone, Clare Rock, Annie Voskertchian, Sujan C. Reddy, Anthony D. Harris
Journal: JAMA Network Open (2021)

Risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care personnel (HCP) are unclear.
Discovery, Learning, and Experimentation With Artificial Intelligence–Based Tools at the Point of Care—Perils and Opportunity
Authors: Andrew Auerbach, Stephan D Fihn
Journal: JAMA Network Open (2021)

Baptiste Vasey, MMed; Stephan Ursprung, MMed; Benjamin Beddoe, BSc; Elliott H. Taylor, BSc; Neale Marlow, MBBS; Nicole Bilbro, MD; Peter Watkinson, MD; Peter McCulloch, MD
Oxygen and oxaliplatin-loaded nanoparticles combined with photo-sonodynamic inducing enhanced immunogenic cell death in syngeneic mouse models of ovarian cancer
Authors: Jiao Zheng, Jiangchuan Sun, Jia Chen, Shenyin Zhu, Shuning Chen, Yujiao Liu, Lan Hao, Zhigang Wang, Shufang Chang
Journal: Journal of Controlled Release (2021)
Abstract 16876: Saturated Arterial Vasoconstriction in the Fontan Circulation
Authors: Hirofumi Saiki, Seiko Kuwata, Manabu Takanashi, Kenji Sugamoto, Hideaki Senzaki
Journal: Circulation (2018)

Background: Cardiac afterload in the Fontan circulation is enhanced due to sequentially connected pulmonary circulation to the systemic circulation. As the augmentation of afterload, which includes both of venous and arterial components, markedly compromise stroke volume in the Fontan patients, identification of primary culprit is vitally important to determine therapeutic targets in preserving circulation and end-organ function. We tested our hypothesis that the augmentation of cardiac afterload in the Fontan circulation is attributed by the compensative arterial constriction in addition to the venous congestion. Methods: Transient inferior vena-caval occlusion (IVCO) was applied to induced venous congestion in 23 Fontan and 87 postoperative biventricular circulation patients(BVC), and augmentation of arterial elastance (Ea) was measured with constructing ventricular pressure-volume relationship. Results: As compared with BVC patients, lower cardiac output in the Fontan patient was attributed by the augmented afterload with similar contractile function. While increase of CVP was augmented in the Fontan pts as compared to those with BVC (p=0.0016), increase of Ea was similar in both groups, suggesting suppressed response of increasing Ea in the Fontan pts. This was further supported by the negative relationship between CVP increase and Ea augmentation (p=0.048). Consistent with this, increase of Ea by induced venous congestion was negatively correlated with mean circulatory filling pressure (p=0.025) as well as systemic vascular resistance (p=0.047). Importantly, augmentation of Ea was independent of renin-angiotensin-aldosterone system (RAAS). Conclusions: Augmentation of afterload by induced venous congestion was rather saturated in the Fontan circulation, suggesting chronic activation of excessive compensatory vasoconstriction at baseline, which involves entire vascular system. As this response was independent of RAAS activity, in addition to RAAS blockade, structural and functional interventions to suppress cardiovascular remodeling should be implemented for the further reduction of cardiac afterload.
CDC Interim Recommendations for Fully Vaccinated People
Authors: Athalia Christie, Sarah A. Mbaeyi, Rochelle P. Walensky
Journal: JAMA (2021)

This Viewpoint summarizes CDC activity recommendations for individuals fully vaccinated against SARS-CoV-2 infection, including resumption of low-risk gatherings among vaccinated people and maintenance of public health measures in activities involving unvaccinated people.
TNF‐α‐Induce Protein 8–Like 1 Inhibits Hepatic Steatosis, Inflammation, and Fibrosis by Suppressing Polyubiquitination of Apoptosis Signal–Regulating Kinase 1
Authors: Hong Wu, Xiaolei Xu, Ancheng Zheng, Weina Wang, Li Mei, Yue Chen, Shasha Sun, Liujun Jiang, Yutao Wu, Yijiang Zhou, Min Zheng, Qishan Chen
Journal: Hepatology (2021)

Background and Aims Characterized by hepatocyte steatosis, inflammation, and fibrosis, NASH is a complicated process that contributes to end‐stage liver disease and, eventually, HCC. TNF‐α‐induced protein 8–like 1 (TIPE1), a new member of the TNF‐α‐induced protein 8 family, has been explored in immunology and oncology research; but little is known about its role in metabolic diseases. Approach and Results Here, we show that hepatocyte‐specific deletion of TIPE1 exacerbated diet‐induced hepatic steatosis, inflammation, and fibrosis as well as systemic metabolic disorders during NASH pathogenesis. Conversely, hepatocyte‐specific overexpression of TIPE1 dramatically prevented the progression of these abnormalities. Mechanically, TIPE1 directly interacted with apoptosis signal–regulating kinase 1 (ASK1) to suppress its TNF receptor–associated factor 6 (TRAF6)–catalyzed polyubiquitination activation upon metabolic challenge, thereby inhibiting the downstream c‐Jun N‐terminal kinase and p38 signaling pathway. Importantly, dramatically reduced TIPE1 expression was observed in the livers of patients with NAFLD, suggesting that TIPE1 might be a promising therapeutic target for NAFLD and related metabolic diseases. Conclusions TIPE1 protects against hepatic steatosis, inflammation, and fibrosis through directly binding ASK1 and restraining its TRAF6‐catalyzed polyubiquitination during the development of NASH. Therefore, targeting TIPE1 could be a promising therapeutic approach for NAFLD treatment.
Oral biofilms revisited: A novel host tissue of bacteriological origin
Authors: Richard P. Darveau, Michael A. Curtis
Journal: Periodontology 2000 (2021)

Abstract The central theme of this volume of Periodontology 2000 is that the microbial dental plaque biofilm, specifically the subgingival dental plaque biofilm, mimics a human tissue in both structure and function. As a basis for this assertion we use the definition of a tissue as an aggregate of similar cells and cell products forming a defined structure with a specific function, in a multicellular organism. Accordingly, we propose that the dental plaque biofilm represents an acquired human tissue largely of bacterial origin that maintains the health of gingival tissue. Furthermore, we acknowledge that disease can be defined as a deviation from the normal structure or an interruption to the function of any body part, organ, or system, and that is manifested by a characteristic set of symptoms and signs whose etiology, pathology, and prognosis may be known or unknown. Therefore, in this volume we present the concept that periodontitis is a disruption of the normal function of the healthy subgingival plaque biofilm with concomitant disruption to its functional properties in relation to innate defense surveillance and tissue maintenance, leading to excessive, deregulated inflammation and tissue destruction.
Associations between plasma cytokine levels and gut microbiota composition in metastatic renal cell carcinoma (mRCC).
Authors: Alex Chehrazi-Raffle, Nazli Dizman, Paulo Gustavo Bergerot, Misagh Karimi, Joann Hsu, John D Gillece, Megan Folkerts, Lauren J Reining, Sarah K Highlander, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2021)

351 Background: Plasma cytokines and the gut microbiome have been shown separately to influence the response to systemic therapy in mRCC. We sought associations between serum cytokines and gut microbial composition in patients (pts) with mRCC. Methods: Eligibility requirements included histologically proven mRCC and an intent to receive either vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) or immune checkpoint inhibitor (ICI). Blood samples were collected prior to treatment initiation and immunologic profiles were evaluated using a Human Cytokine 30-plex protein assay (Invitrogen). Stool was collected at baseline and shotgun metagenomic sequencing was performed to quantify gut microbial populations using previously published methods (Salgia et al Eur Urol 2020). Results: A total of 50 pts were studied (36:14 M:F) with a median age of 67 (range, 32-85). Twenty pts and 30 pts had subsequent initiation of VEGF-TKI and ICI therapy, respectively. Levels of Akkermansia spp were significantly higher in pts who were IL-6 low (P = 0.023). In contrast, pts who were IL-6 high had higher levels of enteric pathogens, including Salmonella spp and Enterococcus spp. Both Akkermansia spp and Bacteroides spp levels were higher in pts who were IL-8 low. Associations between cytokine levels, microbiome composition, and treatment response will be presented. Conclusions: Given studies suggesting the role of Akkermansia spp in enhancing ICI response (Routy et al Science 2018), our data provide a critical link between the gut microbiome and systemic immunomodulation.
The efficacy of omalizumab treatment in chronic spontaneous urticaria is associated with basophil phenotypes
Authors: Kirti J. Johal, Kristin L. Chichester, Eric T. Oliver, Kelly C. Devine, Anja P. Bieneman, John T. Schroeder, Donald W. MacGlashan, Sarbjit S. Saini
Journal: Journal of Allergy and Clinical Immunology (2021)