tbuckley/cabot-search huggingface dataset:
P76.03 Efficacy and Safety of Capmatinib Plus Nivolumab in Pretreated Patients with EGFR Wild-Type Non–Small Cell Lung Cancer
Authors: E. Felip, V. Minotti, D. Tan, J. Wolf, M. Mark, M. Boyer, B. Hughes, A. Bearz, D. Moro-Sibilot, X. Le, J. Vazquez, B. Massuti, N. Liu, L. Hao, Y. Cheng, R. Tiedt, M. Cobo
Journal: Journal of Thoracic Oncology (2021)
P75.14 Gender-Related Safety and Outcome in Advanced NSCLC Patients Treated with Immune Checkpoint-Inhibitors. A Real-World Experience
Authors: P. Pizzutilo, A. Catino, M. Montrone, V. Longo, D. Ricci, F. Pesola, I. Marech, A. Mastrandrea, P. Petrillo, A. Zacheo, N. Varesano, V. Lamorgese, D. Bafunno, D. Galetta
Journal: Journal of Thoracic Oncology (2021)
Ethics Consultation in U.S. Hospitals: A National Follow-Up Study
Authors: Ellen Fox, Marion Danis, Anita J. Tarzian, Christopher C. Duke
Journal: The American Journal of Bioethics (2021)

A 1999-2000 national study of U.S. hospitals raised concerns about ethics consultation (EC) practices and catalyzed improvement efforts. To assess how practices have changed since 2000, we administered a 105-item survey to "best informants" in a stratified random sample of 600 U.S. general hospitals. This primary article details the methods for the entire study, then focuses on the 16 items from the prior study. Compared with 2000, the estimated number of case consultations performed annually rose by 94% to 68,000. The median number of consults per hospital was unchanged at 3, but more than doubled for hospitals with 400+ beds. The level of education of EC practitioners was unchanged, while the percentage of hospitals formally evaluating their ECS decreased from 28.0% to 19.1%. The gap between large, teaching hospitals and small, nonteaching hospitals widened since the prior study. We suggest targeting future improvement efforts to hospitals where needs are not being met by current approaches to EC.
HSR21-067: What Patient-Reported Outcomes Are Being Used in Non-small Cell Lung Cancer? A Targeted Literature Review of Randomized Clinical Trials and Regulatory Labeling
Authors: Kajal Patel, Soham Shukla, Jennifer Hanlon, Kelly Bell, Laurie Eliason, Cosmina Hogea
Journal: Journal of the National Comprehensive Cancer Network (2021)

"HSR21-067: What Patient-Reported Outcomes Are Being Used in Non-small Cell Lung Cancer? A Targeted Literature Review of Randomized Clinical Trials and Regulatory Labeling" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Comment on Garofolo et al. Insulin Resistance and Risk of Major Vascular Events and All-Cause Mortality in Type 1 Diabetes: A 10-Year Follow-up Study. Diabetes Care 2020;43:e139–e141
Authors: José-Miguel González-Clemente, Gemma Llauradó, Lara Albert, Olga Giménez-Palop, Eugenia Berlanga, Joan Vendrell
Journal: Diabetes Care (2021)

Garofolo et al. (1) reported that insulin resistance (IR) is an independent predictor of cardiovascular events and coronary artery disease after adjustment for multiple cofounders including diabetic kidney disease in a 10-year prospective cohort study of 774 patients with type 1 diabetes (T1D). They assessed IR by calculating the estimated glucose disposal rate (eGDR) using the previously validated equation of the Pittsburgh Epidemiology of Diabetes Complication (EDC) Study, which includes only three variables: waist circumference, hypertension, and glycated hemoglobin (HbA1c) (the lower the eGDR, the higher the IR) (1,2). They concluded that such a practicable clinical variable could improve cardiovascular risk stratification in T1D. Nonetheless, they did not attempt to further simplify the …
BPI21-003: Analysis of NAPBC Accreditation Data From a Multi-Disciplinary Accredited Unit in JHB SA Shows That Tumour Biology Not Stage Dictates Treatment Choice With an Increasing Use of Neo-Adjuvant Chemotherapy (NACT)
Authors: Carol-Ann Benn, Bernardo Rapoport, Yastira Ramdas, Barend van den Bergh, Dominic van Loggerenberg, Vernon Shaw
Journal: Journal of the National Comprehensive Cancer Network (2021)

"BPI21-003: Analysis of NAPBC Accreditation Data From a Multi-Disciplinary Accredited Unit in JHB SA Shows That Tumour Biology Not Stage Dictates Treatment Choice With an Increasing Use of Neo-Adjuvant Chemotherapy (NACT)" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Emerging pathogenic role of peripheral blood factors following BBB disruption in neurodegenerative disease
Authors: Min-Tae Jeon, Kyu-Sung Kim, Eun Seon Kim, Suji Lee, Jieun Kim, Hyang-Sook Hoe, Do-Geun Kim
Journal: Ageing Research Reviews (2021)

The responses of central nervous system (CNS) cells such as neurons and glia in neurodegenerative diseases (NDs) suggest that regulation of neuronal and glial functions could be a strategy for ND prevention and/or treatment. However, attempts to develop such therapeutics for NDs have been hindered by the challenge of blood-brain barrier (BBB) permeability and continued constitutive neuronal loss. These limitations indicate the need for additional perspectives for the prevention/treatment of NDs. In particular, the disruption of the blood-brain barrier (BBB) that accompanies NDs allows brain infiltration by peripheral factors, which may stimulate innate immune responses involved in the progression of neurodegeneration. The accumulation of blood factors like thrombin, fibrinogen, c-reactive protein (CRP) and complement components in the brain has been observed in NDs and may activate the innate immune system in the CNS. Thus, strengthening the integrity of the BBB may enhance its protective role to attenuate ND progression and functional loss. In this review, we describe the innate immune system in the CNS and the contribution of blood factors to the role of the CNS immune system in neurodegeneration and neuroprotection.
Plant derived flavonoids induced proteolytic activities of calpain and caspase-3 for apoptosis in human malignant glioblastoma U87MG cells
Authors: Arabinda Das, Surajit Karmakar, Robert K. Stuart, Sunil J. Patel, Naren L. Banik, Swapan K. Ray
Journal: Cancer Research (2005)

3072  Recently, considerable research attention has been focused on identification of naturally occurring chemopreventive substances capable of inhibiting, retarding, or reversing the multi-stage carcinogenesis. A wide array of plant derived polyphenolic compounds has been reported to own substantial anti-mutagenic and anti-carcinogenic activities. The majority of these naturally occurring polyphenolic compounds have potent anti-inflammatory properties, which appear to contribute to their chemopreventive or chemotherapeutic actions. Human malignant glioblastoma is a deadly brain cancer that continues to defy all current therapeutic strategies. So, innovative therapeutic strategies need to be explored for treating this deadly disease. We induced apoptosis in human malignant glioblastoma U87MG cells following exposure to apigenin (APG, a flavonoid present in fruits), (−)-epigallocatechin (EGC, a polyphenol from green tea), (−)-epigallocatechin-3-gallate (EGCG, another polyphenol from green tea), and genistein (GST, an isoflavonoid found in soyabin). Dose-response studies indicated a decrease in cell viability with an increasing dose of APG, EGC, EGCG, or GST. Wright staining and light microscopy for morphology detected predominantly apoptotic features in U87MG cells following exposure to 100 μM APG, 50 μM EGC, 50 μM EGCG, or 100 μM GST for 24 h. Determination of intracellular free Ca2+ levels by fura-2 assay suggested an association of flavonoid induced increase in intracellular free Ca2+ level with apoptosis in U87MG cells. Levels of transcriptional expression (mRNA) of the inhibitor-of-apoptosis proteins (IAPs), also currently designated as the baculovirus IAP repeat containing (BIRC) proteins, were determined by the reverse transcriptase-polymerase chain reaction (RT-PCR). In addition to the RT-PCR experiments, Western blot analyses were performed to determine the protein level expression of the selective BIRC proteins. Western blot analyses also showed alterations in expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins resulting in an increase in Bax:Bcl-2 ratio, and overexpression of calpain and caspase-3 that were also activated to cleave 270 kD α-spectrin at the specific tsites for generation of 145 kD spectrin break down product (SBDP) and 120 kD SBDP, repectively, in course of flavonoid induced apoptosis in U87MG cells. A colorimetric assay using synthetic peptide substrate specific for caspase-3 activity further confirmed the activation of caspase-3 in apoptotic cells. Taken together, all the results from this investigation strongly suggest that the selective plant derived flavonoids are potential therapeutic agents for the induction of apoptotic death in human glioblastoma cells. This investigation was supported in part by the R01 grants from the NCI and NINDS (Bethesda, MD), and also a grant from the State of SC.
EZH2 inhibition activates a dsRNA–STING–interferon stress axis that potentiates response to PD-1 checkpoint blockade in prostate cancer
Authors: Katherine L. Morel, Anjali V. Sheahan, Deborah L. Burkhart, Sylvan C. Baca, Nadia Boufaied, Yin Liu, Xintao Qiu, Israel Cañadas, Kevin Roehle, Max Heckler, Carla Calagua, Huihui Ye, Constantia Pantelidou, Phillip Galbo, Sukanya Panja, Antonina Mitrofanova, Scott Wilkinson, Nichelle C. Whitlock, Shana Y. Trostel, Anis A. Hamid, Adam S. Kibel, David A. Barbie, Atish D. Choudhury, Mark M. Pomerantz, Christopher J. Sweeney, Henry W. Long, David J. Einstein, Geoffrey I. Shapiro, Stephanie K. Dougan, Adam G. Sowalsky, Housheng Hansen He, Matthew L. Freedman, Steven P. Balk, Massimo Loda, David P. Labbé, Brian M. Olson, Leigh Ellis
Journal: Nature Cancer (2021)
P86.21 Activating IDH Mutation as Resistance Mechanism to EGFR TKI in EGFR+ NSCLC
Authors: S. Chen, H. Zhu, M. Jin, Z. Liu, J. Li, C. Hong, T. Li, X. Zhu, L. Meng, D. Qi, X. Zhang, T. Ma, L. Dong, L. Teng, X. Li
Journal: Journal of Thoracic Oncology (2021)
IFNα Augments Clinical Efficacy of Regulatory T-cell Depletion with Denileukin Diftitox in Ovarian Cancer
Authors: Suzanne R. Thibodeaux, Brian B. Barnett, Srilakshmi Pandeswara, Shawna R. Wall, Vincent Hurez, Vinh Dao, Lishi Sun, Benjamin J. Daniel, Michael J. Brumlik, Justin Drerup, Álvaro Padrón, Teresa Whiteside, Ilona Kryczek, Weiping Zou, Tyler J. Curiel
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Immunotherapy treats some cancers, but not ovarian cancer. Regulatory T cells (Tregs) impede anti-ovarian cancer immunity but effective human Treg-directed treatments are lacking. We tested Treg depletion with denileukin diftitox (DD) ± IFNα as ovarian cancer immunotherapy. Patients and Methods: Mice with syngeneic ID8 ovarian cancer challenge were treated with DD, IFNα, or both. The phase 0/I trial tested one dose-escalated DD infusion for functional Treg reduction, safety, and tolerability. The phase II trial added IFNα2a to DD if DD alone failed clinically. Results: DD depleted Tregs, and improved antitumor immunity and survival in mice. IFNα significantly improved antitumor immunity and survival with DD. IFNα did not alter Treg numbers or function but boosted tumor-specific immunity and reduced tumor Treg function with DD by inducing dendritic cell IL6. DD alone was well tolerated, depleted functional blood Tregs and improved immunity in patients with various malignancies in phase 0/I. A patient with ovarian cancer in phase 0/I experienced partial clinical response prompting a phase II ovarian cancer trial, but DD alone failed phase II. Another phase II trial added pegylated IFNα2a to failed DD, producing immunologic and clinical benefit in two of two patients before a DD shortage halt. DD alone was well tolerated. Adding IFNα increased toxicities but was tolerable, and reduced human Treg numbers in blood, and function through dendritic cell–induced IL6 in vitro. Conclusions: Treg depletion is clinically useful but unlikely alone to cure ovarian cancer. Rational treatment agent combinations can salvage clinical failure of Treg depletion alone, even when neither single agent provides meaningful clinical benefit.
Addressing Complementary and Alternative Medicine Use Among Individuals With Cancer: An Integrative Review and Clinical Practice Guideline
Authors: Lynda G Balneaves, Cody Z Watling, Emilie N Hayward, Brenda Ross, Jill Taylor-Brown, Antony Porcino, Tracy L O Truant
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Complementary and alternative medicine (CAM) use is common among individuals with cancer, but many choose not to discuss CAM with health-care providers (HCPs). Moreover, there is variability in the provision of evidence-informed decision making about CAM use. A clinical practice guideline was developed to standardize how oncology HCPs address CAM use as well as to inform how individuals with cancer can be supported in making evidence-informed decisions about CAM. An integrative review of the literature, from inception to December 31, 2018, was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and AMED databases. Eligible articles included oncology HCPs’ practice related to discussing, assessing, documenting, providing decision support, or offering information about CAM. Two authors independently searched the literature, and selected articles were summarized. Recommendations for clinical practice were formulated from the appraised evidence and clinical experiences of the research team. An expert panel reviewed the guideline for usability and appropriateness and recommendations were finalized. The majority of the 30 studies eligible for inclusion were either observational or qualitative, with only 3 being reviews and 3 being experimental. From the literature, 7 practice recommendations were formulated for oncology HCPs regarding how to address CAM use by individuals with cancer, including communicating, assessing, educating, decision coaching, documenting, active monitoring, and adverse event reporting. It is imperative for safe and comprehensive care that oncology HCPs address CAM use as part of standard practice. This clinical practice guideline offers directions on how to support evidence-informed decision making about CAM among individuals with cancer.
Abstract #1871: Autophagy regulation of HMGB1 release from dying tumor cells
Authors: Jacqueline Thorburn, Andrew Thorburn
Journal: Cancer Research (2009)

The characteristics of tumor cell killing by an anti-cancer agent can determine the long-term effectiveness of the treatment. For example, if dying tumor cells release the immune modulator HMGB1 after treatment with anti-cancer drugs, they can activate a tumor-specific immune response that boosts the effectiveness of the initial treatment. We recently found that in response to tumor cell killing by an Epidermal Growth Factor-Receptor-targeted toxin, the induction of autophagy controls whether or not HMGB1 is released from dying tumor cells. Here we have examined the mechanism by which autophagy controls HMGB1 release in other tumor cells and the role of this mechanism in regulating the ability of other anti-cancer agents treat tumor cells. We found that as with the EGFR-targeted toxin, autophagy regulates HMGB1 after treatment with other anti-cancer agents including doxorubicin. These data identify a new function for autophagy during tumor cell killing by anti-cancer agents and open up the possibility of manipulating autophagy during cancer treatment as a way to influence the immunogenicity of the dying tumor cells.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1871.
GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein
Authors: Mai Nakamura, Yuhan Li, Bo-Ran Choi, Elisa Matas-Rico, Juan Troncoso, Chiaki Takahashi, Shanthini Sockanathan
Journal: Science Translational Medicine (2021)

A disintegrin and metalloprotease 10 (ADAM10) is the α-secretase for amyloid precursor protein (APP). ADAM10 cleaves APP to generate neuroprotective soluble APPα (sAPPα), which precludes the generation of Aβ, a defining feature of Alzheimer's disease (AD) pathophysiology. Reduced ADAM10 activity is implicated in AD, but the mechanisms mediating ADAM10 modulation are unclear. We find that the plasma membrane enzyme glycerophosphodiester phosphodiesterase 2 (GDE2) stimulates ADAM10 APP cleavage by shedding and inactivating reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a glycosylphosphatidylinositol (GPI)-anchored inhibitor of ADAM10. In AD, membrane-tethered RECK is highly elevated and GDE2 is abnormally sequestered inside neurons. Genetic ablation of GDE2 phenocopies increased membrane RECK in AD, which is causal for reduced sAPPα, increased Aβ, and synaptic protein loss. RECK reduction restores the balance of APP processing and rescues synaptic protein deficits. These studies identify GDE2 control of RECK surface activity as essential for ADAM10 α-secretase function and physiological APP processing. Moreover, our results suggest the involvement of the GDE2-RECK-ADAM10 pathway in AD pathophysiology and highlight RECK as a potential target for therapeutic development.
Health wearable devices for weight and BMI reduction in individuals with overweight/obesity and chronic comorbidities: systematic review and network meta-analysis
Authors: Daniel J McDonough, Xiwen Su, Zan Gao
Journal: British Journal of Sports Medicine (2021)

To analyse the comparative effectiveness of different health wearable-based physical activity (PA) promotion intervention strategies against each other and control for reducing body weight and body mass index (BMI) in individuals with overweight/obesity and chronic comorbidities.
Pathogenic variants in TNNC2 cause congenital myopathy due to an impaired force response to calcium
Authors: Martijn van de Locht, Sandra Donkervoort, Josine M de Winter, Stefan Conijn, Leon Begthel, Benno Kusters, Payam Mohassel, Ying Hu, Livija Medne, Colin Quinn, Steven A Moore, A Reghan Foley, Gwimoon Seo, Darren T Hwee, Fady I Malik, Thomas Irving, Weikang Ma, Henk L Granzier, Erik-Jan Kamsteeg, Kalyan Immadisetty, Peter Kekenes-Huskey, José R Pinto, Nicol Voermans, Carsten G Bönnemann, Coen Ac Ottenheijm
Journal: Journal of Clinical Investigation (2021)

Troponin C (TnC) is a critical regulator of skeletal muscle contraction; it binds Ca2+ to activate muscle contraction. Surprisingly, the gene encoding fast skeletal TnC (TNNC2) has not yet been implicated in muscle disease. Here, we report 2 families with pathogenic variants in TNNC2. Patients present with a distinct, dominantly inherited congenital muscle disease. Molecular dynamics simulations suggested that the pathomechanisms by which the variants cause muscle disease include disruption of the binding sites for Ca2+ and for troponin I. In line with these findings, physiological studies in myofibers isolated from patients’ biopsies revealed a markedly reduced force response of the sarcomeres to [Ca2+]. This pathomechanism was further confirmed in experiments in which contractile dysfunction was evoked by replacing TnC in myofibers from healthy control subjects with recombinant, mutant TnC. Conversely, the contractile dysfunction of myofibers from patients was repaired by replacing endogenous, mutant TnC with recombinant, wild-type TnC. Finally, we tested the therapeutic potential of the fast skeletal muscle troponin activator tirasemtiv in patients’ myofibers and showed that the contractile dysfunction was repaired. Thus, our data reveal that pathogenic variants in TNNC2 cause congenital muscle disease, and they provide therapeutic angles to repair muscle contractility.
P01.18 Adjuvant Chemotherapy With Modified Nab-Paclitaxel and Carboplatin for Completely Resected NSCLC: Survival Analysis of FAST-Nab.
Authors: H. Saji, H. Sakai, H. Kimura, T. Miyazawa, H. Marushima, K. Kojima
Journal: Journal of Thoracic Oncology (2021)
Extending the conversation over the immune-related hepatotoxicity: author response to Dr. Gauci <i>et al</i>
Authors: Dimitrios C Ziogas, Helen Gogas
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune-related hepatotoxicity (IRH) remains the subject of many immune-oncology debates due to its challenging diagnosis and management. Although it is currently defined by the restrictive Common Terminology Criteria for Adverse Events (CTCAE), the term of IRH covers a wide range of liver pathologies, including hepatitic, cholangitic, mixed, steatotic and nonspecific patterns of injury. Even when liver biopsy is performed, the recognized histopathological findings cannot predict the response to steroids or the need for secondary immunosuppression, and usually do not significantly modify the suggested empirical treatment of IRH. Beyond the CTCAE grading, a more comprehensive assessment of IRH severity, including laboratory biomarkers and clinical features, should be developed and a more patient-oriented management should be established by additional randomized evidence, incorporating hepatology and immune-oncology experience.
Efficacy and Safety of Diclofenac–Hyaluronate Conjugate (Diclofenac Etalhyaluronate) for Knee Osteoarthritis: A Randomized Phase III Trial in Japan
Authors: Yoshihiro Nishida, Kazuyuki Kano, Yuji Nobuoka, Takayuki Seo
Journal: Arthritis & Rheumatology (2021)

To confirm the efficacy and safety of intraarticular (IA) injection of diclofenac covalently linked to hyaluronic acid (diclofenac etalhyaluronate [DF-HA]; ONO-5704/SI-613) in patients with knee osteoarthritis (OA).In a phase III multicenter, randomized, double-blind, placebo-controlled trial, eligible subjects ages 40-75 years with symptomatic knee OA (Kellgren/Lawrence score of 2 or 3) were randomly assigned to receive IA injections of DF-HA 30 mg or placebo (citric acid-sodium citrate buffered solution; 1:1) once every 4 weeks for 20 weeks (a total of 6 injections). Subjects were followed up for 24 weeks. The primary end point was the mean change from baseline to 12 weeks in Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC) pain subscale scores, measured on a 100-mm visual analog scale. Safety was evaluated by adverse event monitoring.All 440 subjects received investigational products (220 received placebo and 220 received DF-HA). The full analysis set and safety population comprised 438 subjects (220 in the placebo group and 218 in the DF-HA group) and 440 subjects, respectively. At 12 weeks, subjects receiving DF-HA showed significant improvement from baseline in the WOMAC pain subscale score (-23.2 mm) compared to subjects receiving placebo ( -17.1 mm), with a difference of -6.1 mm (95% confidence interval -9.4, -2.8; P < 0.001). The difference between groups was significant as early as week 1, and a difference was maintained for 24 weeks, although the difference at week 24 was not significant. Anaphylactic reactions were observed in 2 subjects receiving DF-HA.Our findings indicate that treatment with DF-HA results in significant improvement in the WOMAC pain subscale score compared to placebo over 12 weeks. Anaphylactic reactions were observed, and further safety evaluation is needed.
P78.16 Real-World Outcomes of Camrelizumab (SHR-1210) in Treating Advanced Non-Small Cell Lung Cancer: A Multicenter Prospective Study
Authors: K. Gu, M. Bi, D. Zhao, H. Cheng, H. Qian, F. Wang, G. Wang, W. Song, X. Xia, L. Xu, Y. Zhu, Q. Cao, X. Li, P. Fang
Journal: Journal of Thoracic Oncology (2021)
P49.01 Treatment Planning QA of Hippocampal Avoidance Prophylactic Cranial Irradiation in the Multicenter Randomized Phase III Trial (NCT01780675)
Authors: O. Candiff, J. Belderbos, E. Damen, P. Van Haaren, W. Crijns, S. Hol, L. Paelinck, J. Jaspers, Z. Van Kesteren, G. De Kerf, W. Van Elmpt, J.F. Ubbels, S. Schagen, D. De Ruysscher, M. De Ruiter
Journal: Journal of Thoracic Oncology (2021)
P76.14 Time to First Progression in Patients with NSCLC with Brain Metastases Receiving 3rd Generation TKI alone vs TKI + Brain Radiation
Authors: N. Thomas, N. Myall, F. Sun, T. Patil, R. Mushtaq, C. Yu, E. Pollom, S. Nagpal, R. Camidge, C. Rusthoven, S. Braunstein, H.A. Wakelee, C. Mccoach
Journal: Journal of Thoracic Oncology (2021)